whole-body-nanoparticle-aerosol-inhalation-exposures

Whole-Body Nanoparticle Aerosol Inhalation Exposures

Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle ...

West Virginia University 

Epidemiological evidence indicates that environmental air pollutants are positively associated with the development of chronic vascular disease; however, the mechanisms involved have not been fully elucidated. In the present study we examined molecular pathways associated with chronic vascular disease in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice, including markers of vascular remodeling and oxidative stress, in response to exposure to the ubiquitous environmental pollutant, gasoline engine emissions. ApoE(-/-) mice, on a high-fat diet, were exposed by inhalation to either filtered air; 8, 40, or 60 mug/m(3) particulate matter whole exhaust; or filtered exhaust with gases matching the 60-mug/m(3) concentration, for 7 weeks. Aortas and plasma were collected and assayed for changes in histochemical markers, real-time reverse transcriptase-polymerase chain reaction, and indicators of oxidative damage. Inhalational exposure to gasoline engine emissions resulted in increased aortic mRNA expression of matrix metalloproteinase-3 (MMP-3), MMP-7, and MMP-9, tissue inhibitor of metalloproteinases-2, endothelin-1 and heme oxygenase-1 in ApoE(-/-) mice; increased aortic MMP-9 protein levels were confirmed through immunohistochemistry. Elevated reactive oxygen species were also observed in arteries from exposed animals, despite absence of plasma markers. Similar findings were also observed in the aortas of ApoE(-/-) mice exposed to particle-filtered atmosphere, implicating the gaseous components of the whole exhaust in mediating the expression of markers associated with the vasculopathy. These findings demonstrate that exposure to gasoline engine emissions results in the transcriptional upregulation of factors associated with vascular remodeling, as well as increased markers of vascular oxidative stress, which may contribute to the progression of atherosclerosis and reduced stability of vulnerable plaques.

Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis.

Preuves &eacute;pid&eacute;miologiques indiquent que les polluants environnementaux sont positivement associ&eacute;es au d&eacute;veloppement d&#39;une maladie vasculaire chronique ; Cependant, les m&eacute;canismes impliqu&eacute;s n&#39;ont pas &eacute;t&eacute; enti&egrave;rement &eacute;lucid&eacute;s. Dans la pr&eacute;sente &eacute;tude, nous avons examin&eacute; les voies mol&eacute;culaires associ&eacute;s &agrave; des maladies vasculaires chroniques dans le sujette &agrave; l&#39;ath&eacute;roscl&eacute;rose apolipoprot&eacute;ine E-deficient (ApoE(-/-)) de la souris, y compris les marqueurs du remodelage vasculaire et le stress oxydatif, en r&eacute;ponse &agrave; l&#39;exposition au polluant environnemental omnipr&eacute;sent, les &eacute;missions des moteurs essence. ApoE(-/-) souris, sur un r&eacute;gime alimentaire riche en graisses, ont &eacute;t&eacute; expos&eacute;s par inhalation &agrave; l&#39;air soit filtr&eacute; ; 8, 40 ou 60 mug/m(3) particules ensemble &eacute;chappement ; ou filtr&eacute;e d&#39;&eacute;chappement avec gaz correspondant &agrave; la concentration de 60-mug/m(3), pendant 7 semaines. Les aortes et plasma ont &eacute;t&eacute; recueillis et analys&eacute;s pour changements histochimiques marqueurs, la transcriptase inverse-PCR en temps r&eacute;el et indicateurs de dommages oxydatifs. Exposition par inhalation aux &eacute;missions des moteurs essence a entra&icirc;n&eacute; une augmentation aortique expression de l&#39;ARNm de matrice m&eacute;talloprot&eacute;inase-3 (MMP-3), MMP-7 et MMP-9, inhibiteur tissulaire de m&eacute;talloprot&eacute;inase-2, l&#39;endoth&eacute;line-1 et h&egrave;me oxyg&eacute;nase-1 chez les souris ApoE(-/-) ; niveaux de prot&eacute;ine MMP-9 aortiques accrus &eacute;taient confirm&eacute;es par immunohistochimie. Esp&egrave;ces oxyg&eacute;n&eacute;es &eacute;lev&eacute;es ont aussi &eacute;t&eacute; observ&eacute;s dans les art&egrave;res des animaux expos&eacute;s, malgr&eacute; l&#39;absence de marqueurs de plasma. Des r&eacute;sultats similaires ont aussi &eacute;t&eacute; observ&eacute;s dans les aortes de ApoE(-/-) souris expos&eacute;s &agrave; l&#39;atmosph&egrave;re de particules filtr&eacute;es, impliquant les constituants gazeux de l&#39;&eacute;chappement entier dans la m&eacute;diation de l&#39;expression des marqueurs associ&eacute;s de la vasculopathie. Ces r&eacute;sultats d&eacute;montrent que l&#39;exposition aux r&eacute;sultats des &eacute;missions moteurs essence dans la r&eacute;gulation transcriptionnelle des facteurs associ&eacute;s &agrave; un remodelage vasculaire, ainsi que des marqueurs une augmentation du stress oxydatif vasculaire, ce qui peut contribuer &agrave; la progression de l&#39;ath&eacute;roscl&eacute;rose et de la stabilit&eacute; r&eacute;duite des plaques vuln&eacute;rables.

&Eacute;missions d&#39;&eacute;chappement essence induisent des voies remodelage vasculaires intervenant dans l&#39;ath&eacute;roscl&eacute;rose.

Evidenza epidemiologica indica che inquinanti ambientali sono positivamente associati con lo sviluppo di malattie vascolari croniche; Tuttavia, i meccanismi coinvolti non sono stata completamente chiariti. Nel presente studio abbiamo esaminato pathways molecolari associati con malattia vascolare cronica nell&#39;aterosclerosi incline apolipoproteina E-carenti (ApoE(-/-)) topi, inclusi i marcatori di rimodellamento vascolare e lo stress ossidativo, in risposta all&#39;esposizione a sostanza inquinante ambientale onnipresente, emissioni dei motori benzina. ApoE(-/-) topi, una dieta ricca di grassi, sono stati esposti per inalazione o aria filtrata; 8, 40 o 60 mug/m(3) particolato intero scarico; o scarico filtrato con gas corrispondente alla concentrazione di 60-mug/m(3), per 7 settimane. Aortas e plasma sono stati raccolti e analizzati per i cambiamenti nei marcatori istochimici, Real-Time reverse transcriptase-polymerase chain reaction e indicatori di danno ossidativo. Da inalazione esposizione alle emissioni dei motori benzina portato a maggiore espressione del mRNA dell&#39;aorta di matrix metalloproteinase-3 (MMP-3), MMP-7 e MMP-9, tessuto inibitore della metalloproteinasi-2, endotelina-1 ed eme ossigenasi-1 nei topi ApoE(-/-); aumentati livelli di proteina MMP-9 aortico sono stati confermati mediante immunoistochimica. Specie ossigenate reattive elevati sono state osservate anche nelle arterie da animali esposti, nonostante l&#39;assenza di marcatori di plasma. Risultati simili sono stati osservati anche in aortas di ApoE(-/-) topi esposti all&#39;atmosfera delle particelle filtrate, implicando i componenti gassosi del gas di scarico tutto nella mediazione l&#39;espressione di marcatori associati con la vasculopatia. Questi risultati dimostrano che l&#39;esposizione a benzina motore emissioni risultati nella sovraregolazione di transcriptional di fattori associati con rimodellamento vascolare, cos&igrave; come marcatori di aumentati dello stress ossidativo vascolare, che possono contribuire alla stabilit&agrave; ridotta delle placche vulnerabili e la progressione dell&#39;aterosclerosi.

Le emissioni di gas di scarico benzina inducono percorsi rimodellamento vascolare coinvolti nell&#39;aterosclerosi.

Epidemiological studies have shown a positive association between exposure to air particulate matter (PM) pollution and adverse cardiovascular health effects in susceptible subpopulations such as those with pre-existing cardiovascular disease. The mechanism(s) through which pulmonary deposited PM, particularly fine PM2.5, PM with mass median aerodynamic diameter <2.5 microm, affects the cardiovascular system is currently not known and remains a major focus of investigation. In the present study, the transcriptosome and transcription factor proteome were examined in rat neonatal cardiomyocyte (RCM) cultures, following an acute exposure to bioavailable constituents of PM2.5 oil combustion particles designated residual oil fly ash leachate (ROFA-L). Out of 3924 genes examined, 38 genes were suppressed and 44 genes were induced following a 1-h exposure to 3.5 microg/ml of a particle-free leachate of ROFA (ROFA-L). Genomic alterations in pathways related to IGF-1, VEGF, IL-2, PI3/AKT, cardiovascular disease, and free radical scavenging, among others, were detected 1 h postexposure to ROFA-L. Global gene expression was altered in a manner consistent with cardiac myocyte electrophysiological remodeling, cellular oxidative stress, and apoptosis. ROFA-L altered the transcription factor proteome by suppressing activity of 24 and activating 40 transcription factors out of a total of 149. Genomic alterations were found to correlate with changes in transcription factor proteome. These acute changes indicate pathological molecular alterations, which may lead to possible chronic alterations to the cardiac myocyte. These data also potentially relate underlying cardiovascular effects from occupational exposure to ROFA and identify how particles from specific emission sources may mediate ambient PM cardiac effects.

Fine oil combustion particle bioavailable constituents induce molecular profiles of oxidative stress, altered function, and cellular injury in cardiomyocytes.

Des &eacute;tudes &eacute;pid&eacute;miologiques ont montr&eacute; une association positive entre l&#39;exposition &agrave; la pollution atmosph&eacute;rique de mati&egrave;res particulaires (MP) et d&#39;effets ind&eacute;sirables cardiovasculaires dans les sous-populations sensibles tels que ceux atteints de maladies cardiovasculaires pr&eacute;existants. L&#39;ou les m&eacute;canismes par lesquels pulmonaire d&eacute;pos&eacute; PM, particuli&egrave;rement fines PM2, 5, PM avec un diam&egrave;tre a&eacute;rodynamique moyen en masse &lt; 2,5 microm, influe sur le syst&egrave;me cardiovasculaire n&#39;est pas encore connu et reste un objectif majeur de l&#39;enqu&ecirc;te. Dans la pr&eacute;sent &eacute;tude, la transcriptosome et la transcription facteur proteome ont &eacute;t&eacute; examin&eacute;s dans les cultures de cardiomyocyte n&eacute;onatal (MRC) de rat, apr&egrave;s une exposition aigu&euml; &agrave; biodisponible constituants des particules de combustion de p&eacute;trole PM2, 5 d&eacute;sign&eacute;s lixiviat de cendres volantes de l&#39;huile r&eacute;siduelle (Rudy-L). Hors 3924 g&egrave;nes examin&eacute;s, 38 g&egrave;nes furent supprim&eacute;s et 44 g&egrave;nes ont &eacute;t&eacute; induites par suite d&#39;une exposition de 1 h &agrave; 3,5 microg/ml d&#39;un produit de lixiviation exempt de particule de Rudy (Rudy-L). Alt&eacute;rations g&eacute;nomiques dans les voies associ&eacute;s &agrave; l&#39;IGF-1, VEGF, il-2, PI3/AKT, maladies cardiovasculaires et pi&eacute;geage, entre autres, de radicaux libres ont &eacute;t&eacute; d&eacute;tect&eacute;es &agrave; l&#39;exposition de 1 h &agrave; l&#39;expression des g&egrave;nes Rudy-L. mondiale a &eacute;t&eacute; alt&eacute;r&eacute;e d&#39;une mani&egrave;re compatible avec les myocytes cardiaques remodelage &eacute;lectrophysiologiques, stress oxydatif cellulaire et l&#39;apoptose. Rudy-L modifi&eacute; le prot&eacute;ome de facteur de transcription en supprimant l&#39;activit&eacute; des 24 et en activant des facteurs de transcription 40 sur un total de 149. Alt&eacute;rations g&eacute;nomiques ont &eacute;t&eacute; trouv&eacute;es en corr&eacute;lation avec les changements proteome de facteur de transcription. Ces changements aigus indiquent des alt&eacute;rations mol&eacute;culaires pathologiques, qui peuvent conduire &agrave; d&#39;&eacute;ventuelles alt&eacute;rations chroniques pour le myocyte cardiaque. Ces donn&eacute;es aussi potentiellement concernent sous-jacente des effets cardiovasculaires de l&#39;exposition professionnelle &agrave; Rudy et d&#39;identifient comment les particules provenant de sources sp&eacute;cifiques d&#39;&eacute;mission peuvent servir de m&eacute;diateurs ambiantes effets cardiaques de la PM.

Fines particules huileuses combustion particule biodisponible induisent des profils mol&eacute;culaires du stress oxydatif, la fonction alt&eacute;r&eacute;e et l&eacute;sion cellulaire dans les cardiomyocytes.

Studi epidemiologici hanno dimostrato un&#39;associazione positiva tra esposizione al particolato (PM) inquinamento atmosferico ed effetti avversi sulla salute cardiovascolare in sottopopolazioni sensibili come quelli con preesistente malattia cardiovascolare. I meccanismi comprendono attraverso il quale polmonare depositano PM, particolarmente fine PM2,5, PM con diametro aerodinamico mediano in massa &lt; 2,5 microm, colpisce il sistema cardiovascolare attualmente non &egrave; noto e rimane un importante focus di indagine. Nel presente studio, il transcriptosome e trascrizione proteoma fattore sono stati esaminati in culture di ratto cardiomyocyte neonatale (RCM), dopo un&#39;esposizione acuta a costituenti biodisponibile di PM2,5 olio particelle di combustione indicati olio residuo ceneri percolato (Eddy-L). Fuori 3924 geni esaminati, 38 geni furono soppresse e 44 geni sono stati indotti dopo un esposizione di 1-h 3,5 microg/ml di un particella libera percolato di Eddy (Eddy-L). Alterazioni genomiche in percorsi legati all&#39;IGF-1, VEGF, il-2, PI3/AKT, malattie cardiovascolari e free radical scavenging, tra gli altri, sono stati rilevati postexposure 1 h di espressione genica globale L. Eddy &egrave; stato modificato in maniera coerente con ritocco elettrofisiologico del miocita cardiaco, stress ossidativo cellulare e apoptosi. Eddy-L alterato il proteoma del fattore di trascrizione di sopprimere l&#39;attivit&agrave; del 24 e l&#39;attivazione di fattori di trascrizione 40 su un totale di 149. Alterazioni genomiche sono stati trovati per correlare con le modifiche apportate nel proteoma di fattore di trascrizione. Questi cambiamenti acuti indicano alterazioni molecolari patologiche, che possono portare a possibili alterazioni croniche del myocyte cardiaco. Questi dati anche potenzialmente riguardano gli effetti cardiovascolari sottostanti da esposizione professionale a Eddy e identificano come particelle da fonti di emissione specifiche possono mediare ambientali PM effetti cardiaci.

Raffinato olio combustione delle particelle biodisponibile costituenti inducono profili molecolari di stress ossidativo, alterata funzione e danno cellulare nei cardiomyocytes.

Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 microg/m(3) for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS.

Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS.

Pollution de l&#39;air environnant est associ&eacute;e &agrave; des &eacute;v&eacute;nements ind&eacute;sirables cardiovasculaires, y compris les hospitalisations accrue en raison de l&#39;insuffisance cardiaque et l&#39;infarctus du myocarde. Le m&eacute;canisme exact par lequel la pollution atmosph&eacute;rique affecte le c&oelig;ur et le syst&egrave;me vasculaire est actuellement inconnu. Des &eacute;tudes r&eacute;centes ont montr&eacute; que l&#39;exposition &agrave; l&#39;air la pollution favorise la vasoconstriction art&eacute;rielle chez l&#39;homme et des mod&egrave;les animaux. Travaux dans notre laboratoire ont montr&eacute; que les &eacute;missions de diesel (DE) renforcer la vasoconstriction des art&egrave;res coronaires de souris. Ainsi, nous avons &eacute;mis l&#39;hypoth&egrave;se que DE pourrait am&eacute;liorer la vasoconstriction dans les art&egrave;res et les veines par d&eacute;couplage de monoxyde d&#39;azote synthase endoth&eacute;liale (eNOS). Pour tester cette hypoth&egrave;se, nous d&#39;abord propag&eacute; DE par une solution de s&eacute;rum physiologique et expos&eacute;s des veines m&eacute;sent&eacute;riques isol&eacute;s. Deuxi&egrave;mement, nous expos&eacute;s animaux, tout le corps, &agrave; DE &agrave; 350 microg/m(3) pendant 4 h, apr&egrave;s quoi les veines et les art&egrave;res m&eacute;sent&eacute;riques ont &eacute;t&eacute; isol&eacute;s. Les r&eacute;sultats de ces exp&eacute;riences Voir la saline que barboter avec DE ainsi que par inhalation D&#39;am&eacute;liore la vasoconstriction dans les veines mais pas les art&egrave;res. Exposition de plusieurs compos&eacute;s organiques volatils repr&eacute;sentatifs dans la solution saline DE-exposed n&#39;augmente pas la constriction art&eacute;rielle. L-nitro-arginine-m&eacute;thyl-ester (L-NAME), un inhibiteur de l&#39;eNOS, normalis&eacute; des vaisseaux de contr&ocirc;le pour les navires DE-exposed impliquant un d&eacute;couplage de l&#39;eNOS, comme un m&eacute;canisme de vasoconstriction accrue. Les principales conclusions de cette recherche sont veines 1) pi&egrave;ce suit la dysfonction endoth&eacute;liale in vivo et ex vivo des expositions &agrave; DE, veines 2) semblent &ecirc;tre plus sensibles aux effets DE que les art&egrave;res, et 3) DE composants tr&egrave;s probables provoquent la dysfonction endoth&eacute;liale par le d&eacute;couplage de l&#39;eNOS.

Exposition aux gaz d&#39;&eacute;chappement de diesel rehausse veinoconstriction via le d&eacute;couplage de l&#39;eNOS.

L&#39;inquinamento dell&#39;aria ambientale &egrave; associato con eventi avversi cardiovascolari, compresi ricoveri ospedalieri aumentato a causa di insufficienza cardiaca e infarto del miocardio. I meccanismi comprendono esatto da cui l&#39;inquinamento atmosferico colpisce il cuore e il sistema vascolare sono attualmente sconosciuto. Recenti studi hanno scoperto che l&#39;esposizione all&#39;aria l&#39;inquinamento aumenta la vasocostrizione arteriosa in modelli animali e gli esseri umani. Lavoro presso il nostro laboratorio ha dimostrato che emissioni diesel (DE) migliorano la vasocostrizione delle arterie coronarie del mouse. Cos&igrave;, abbiamo ipotizzato che DE potrebbe migliorare la vasocostrizione in arterie e vene attraverso lo sganciamento di endoteliale di ossido nitrico sintasi (eNOS). Per verificare questa ipotesi, abbiamo prima gorgogliare DE attraverso una soluzione fisiologica ed esposto vene mesenteriche isolate. In secondo luogo, siamo esposti animali, tutto il corpo, a DE a 350 microg/m(3) per 4 ore, dopo di che le vene e le arterie mesenteriche sono state isolate. Risultati di questi esperimenti che salina Visualizza gorgogliare con DE cos&igrave; come inalato DE aumenta la vasocostrizione nelle vene, ma non le arterie. Esposizione a molti composti organici volatili rappresentante trovato nella soluzione salina DE-exposed non ha fatto migliorare la costrizione arteriosa. L-nitro-arginina-metil-estere (L-nome), un inibitore di eNOS, normalizzato le navi di controllo per i vasi DE-exposed, implicando disgiungere di eNOS come un meccanismo per una maggiore vasocostrizione. Le principali conclusioni di questa ricerca sono 1) vene esibiscono segue la disfunzione endoteliale in vivo, ex vivo esposizioni a DE, 2) vene sembrano essere pi&ugrave; sensibili agli effetti DE le arterie, e 3) DE componenti pi&ugrave; probabile inducono disfunzione endoteliale attraverso dello sganciamento di eNOS.

L&#39;esposizione di gas di scarico diesel migliora venoconstriction via disgiungere di eNOS.

Meccanismi di esacerbazione di indotta da inquinamento dell&#39;aria della malattia cardiovascolare sono attualmente sconosciuti, cos&igrave; abbiamo esaminato i ruoli di vascolare endotelina-1 (ET-1) e di specie reattive dell&#39;ossigeno (ROS) nella regolazione di mediatori di rimodellamento vascolare, metalloproteinasi di matrice (MMP), vale a dire dopo l&#39;esposizione alle emissioni del motore di veicolo.

Emissioni veicolari inducono vascolare espressione di MMP-9 e attivit&agrave; associati con percorsi di endotelina-1-mediata.

Mechanisms of air pollution-induced exacerbation of cardiovascular disease are currently unknown, thus we examined the roles of vascular endothelin-1 (ET-1) and reactive oxygen species (ROS) in regulating mediators of vascular remodeling, namely matrix metalloproteinases (MMPs), after exposure to vehicle engine emissions.

Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways.

M&eacute;canismes d&#39;exacerbation d&#39;air induite par la pollution des maladies cardiovasculaires sont actuellement inconnus, donc nous avons examin&eacute; les r&ocirc;les de vasculaire l&#39;endoth&eacute;line-1 (ET-1) et les esp&egrave;ces r&eacute;actives de l&#39;oxyg&egrave;ne (ROS) dans la r&eacute;gulation des m&eacute;diateurs du remodelage vasculaire, &agrave; savoir les m&eacute;talloprot&eacute;inases matricielles (MMP), apr&egrave;s exposition aux &eacute;missions de moteur de v&eacute;hicule.

&Eacute;missions v&eacute;hiculaires induisent l&#39;expression de MMP-9 vasculaire et activit&eacute; associ&eacute;e aux voies induite par l&#39;endoth&eacute;line-1.

Air pollutant levels positively correlate with increases in both acute and chronic cardiovascular disease. The pollutant diesel exhaust (DE) increases endothelin (ET) levels, suggesting that this peptide may contribute to DE-induced cardiovascular disease. We hypothesized that acute exposure to DE also enhances ET-1-mediated coronary artery constrictor sensitivity. Constrictor responses to KCl, U-46619, and ET-1 were recorded by videomicroscopy in pressurized intraseptal coronary arteries from rats exposed for 5 h to DE (300 microg/m(3)) or filtered air (Air). ET-1 constriction was augmented in arteries from DE-exposed rats. Nitric oxide synthase (NOS) inhibition [N(omega)-nitro-L-arginine (L-NNA), 100 microM] and endothelium inactivation augmented ET-1 responses in arteries from Air but not DE rats so that after either treatment responses were not different between groups. DE exposure did not affect KCl and U-46619 constrictor responses, while NOS inhibition augmented KCl constriction equally in both groups. Thus basal NOS activity does not appear to be affected by DE exposure. The endothelin type B (ET(B)) receptor antagonist BQ-788 (10 microM) inhibited ET-1 constriction in DE but not Air arteries, and constriction in the presence of the antagonist was not different between groups. Cytokine levels were not different in plasma from DE and AIR rats, suggesting that acute exposure to DE does not cause an immediate inflammatory response. In summary, a 5-h DE exposure selectively increases constrictor sensitivity to ET-1. This augmentation is endothelium-, NOS-, and ET(B) receptor dependent. These data suggest that DE exposure diminishes ET(B) receptor activation of endothelial NOS and augments ET(B)-dependent vasoconstriction. This augmented coronary vasoreactivity to ET-1 after DE, coupled with previous reports that DE induces production of ET-1, suggests that ET-1 may contribute to the increased incidence of cardiac events during acute increases in air pollution levels.

Impairment of coronary endothelial cell ET(B) receptor function after short-term inhalation exposure to whole diesel emissions.

Les concentrations de polluants a&eacute;riens sont corr&eacute;l&eacute;s positivement avec une augmentation des maladies cardiovasculaires aigu&euml;s et chroniques. L&#39;&eacute;chappement des moteurs diesel polluant (DE) augmente les niveaux de l&#39;endoth&eacute;line (ET), ce qui sugg&egrave;re que ce peptide pourrait contribuer &agrave; des maladies cardiovasculaires DE-induced. Nous avons &eacute;mis l&#39;hypoth&egrave;se que l&#39;exposition aigu&euml; &agrave; DE am&eacute;liore &eacute;galement sensibilit&eacute; constrictor coronarienne induite par l&#39;ET-1. R&eacute;ponses constrictrices au KCl, U-46619 et l&#39;ET-1 ont &eacute;t&eacute; enregistr&eacute;es par vid&eacute;omicroscopie dans les art&egrave;res coronaires intraseptal sous pression des rats expos&eacute;s pendant 5 heures afin DE (300 microg/m(3)) ou air filtr&eacute; (Air). Constriction ET-1 a &eacute;t&eacute; augment&eacute;e dans les art&egrave;res des rats DE-exposed. L&#39;oxyde nitrique synthase (NOS) inhibition [N (om&eacute;ga) - nitro - L-arginine (L-NNA), microM 100] et inactivation de l&#39;endoth&eacute;lium augment&eacute;e r&eacute;ponses ET-1 dans les art&egrave;res de l&#39;Air, mais pas DE rats de sorte que, apr&egrave;s deux r&eacute;actions aux traitements n&#39;&eacute;taient pas diff&eacute;rents entre les groupes. Exposition DE n&#39;a rien de KCl et U-46619 r&eacute;ponses constrictrices, tandis que l&#39;inhibition de NOS augment&eacute;e constriction KCl &eacute;galement dans les deux groupes. Ainsi l&#39;activit&eacute; basale de NOS ne semble pas d&#39;&ecirc;tre affect&eacute;s par l&#39;exposition DE. Le type de l&#39;endoth&eacute;line B (antagoniste des r&eacute;cepteurs ET(B)) BQ-788 (10 microM) inhibe la constriction ET-1 dans le DE, mais pas les art&egrave;res Air et constriction en pr&eacute;sence de l&#39;antagoniste ne diff&eacute;rait pas entre les groupes. Des niveaux de cytokine n&#39;&eacute;taient pas diff&eacute;rentes dans le plasma des rats DE et de l&#39;AIR, ce qui sugg&egrave;re que l&#39;exposition aigu&euml; &agrave; DE provoque une r&eacute;ponse inflammatoire imm&eacute;diate. En r&eacute;sum&eacute;, une exposition de 5 h a s&eacute;lectivement augmente la sensibilit&eacute; constrictor &agrave; l&#39;ET-1. Cette augmentation est l&#39;endoth&eacute;lium - amendements- et ET(B) r&eacute;cepteurs d&eacute;pendants. Ces r&eacute;sultats sugg&egrave;rent que l&#39;exposition DE diminue l&#39;activation des r&eacute;cepteurs ET(B) de NOS endoth&eacute;liales et augmente ET (B)-vasoconstriction d&eacute;pendante. Cela augment&eacute;e vasor&eacute;activit&eacute; coronaire &agrave; l&#39;ET-1, apr&egrave;s le DE, coupl&eacute; avec les rapports pr&eacute;c&eacute;dents que D&#39;induit la production d&#39;ET-1, indique que ET-1 pourrait contribuer &agrave; l&#39;augmentation de l&#39;incidence d&#39;&eacute;v&eacute;nements cardiaques pendant aigu&euml; augmentation des niveaux de pollution atmosph&eacute;rique.

Alt&eacute;ration de la fonction des r&eacute;cepteurs des cellules endoth&eacute;liales coronariennes ET(B) apr&egrave;s une exposition par inhalation &agrave; court terme aux &eacute;missions de diesel enti&egrave;re.

Di inquinanti atmosferici correlano positivamente con un incremento di malattie cardiovascolari sia acuta che cronica. I gas di scarico diesel inquinante (DE) aumenta i livelli di endotelina (ET), suggerendo che questo peptide pu&ograve; contribuire alla malattia cardiovascolare DE-induced. Abbiamo ipotizzato che l&#39;esposizione acuta a DE migliora anche la sensibilit&agrave; constrictor ET-1-mediata dell&#39;arteria coronaria. Risposte di Constrictor di KCl, U-46619 ed ET-1 sono state registrate da videomicroscopy di coronarie intraseptal pressurizzati da ratti esposti per 5 h per DE (300 microg/m(3)) o aria filtrata (aria). Costrizione di ET-1 &egrave; stata aumentata nelle arterie da ratti DE-exposed. Ossido nitrico sintasi (NOS) inibizione [N (omega) - nitro - L-arginina (L-NNA), 100 microM] e inattivazione dell&#39;endotelio aumentata ET-1 risposte nelle arterie dall&#39;aria, ma non DE ratti cos&igrave; che dopo due risposte al trattamento non erano differenti tra i gruppi. DE esposizione non ha influito sulle risposte di constrictor KCl e U-46619, mentre l&#39;inibizione NOS aumentata costrizione KCl ugualmente in entrambi i gruppi. Attivit&agrave; di NOS basale non sembra quindi essere colpiti dall&#39;esposizione DE. Il tipo di endotelina B (antagonista del recettore ET(B)) BQ-788 (10 microM) inibito ET-1 costrizione in DE ma non le arterie aria e costrizione in presenza dell&#39;antagonista non era differente tra i gruppi. Livelli di citochine non erano differenti nel plasma da aria e DE ratti, suggerendo che l&#39;esposizione acuta a DE non provoca una risposta infiammatoria immediata. In sintesi, un&#39;esposizione DE 5-h aumenta in modo selettivo constrictor sensibilit&agrave; di ET-1. Questo aumento &egrave; endotelio - NOS- ed ET(B) recettore dipendente. Questi dati suggeriscono che l&#39;esposizione DE diminuisce l&#39;attivazione del recettore ET(B) di NOS endoteliale e potenzia ET (B)-dipendente vasocostrizione. Questa aumentata coronarica vasoreactivity ET-1 dopo it, accoppiato con precedenti relazioni che DE induce la produzione di ET-1, suggerisce che ET-1 pu&ograve; contribuire per l&#39;aumento dell&#39;incidenza di eventi cardiaci durante acuta aumenta a livelli di inquinamento dell&#39;aria.

Compromissione della funzione di recettore delle cellule endoteliali coronariche ET(B) dopo l&#39;esposizione a breve termine di inalazione per emissioni diesel intero.

Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology. Apolipoprotein E-null mice were simultaneously placed on a high-fat chow diet and exposed to four concentrations, plus a high concentration exposure with particulates (PM) removed by filtration, of diesel emissions for 6 h/day for 50 days. Aortas were subsequently assayed for alterations in matrix metalloproteinase-9, endothelin-1, and several other biomarkers. Diesel induced dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation; filtration of PM did not significantly alter these vascular responses, indicating that the gaseous portion of the exhaust was a principal driver. Immunohistochemical analysis of aortic leaflet sections revealed no net increase in lesion area, but a significant decrease in lipid-rich regions and increasing trends in macrophage accumulation and collagen content, suggesting that plaques were advanced to a more fragile, potentially more vulnerable state by diesel exhaust exposure. Combined with previous studies, these results indicate that whole emissions from mobile sources may have a significant role in promoting chronic vascular disease.

Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-) mice.

Des &eacute;tudes &eacute;pid&eacute;miologiques r&eacute;centes sugg&egrave;rent que la pollution atmosph&eacute;rique li&eacute;e au trafic peut-&ecirc;tre avoir des effets n&eacute;fastes sur la sant&eacute; cardiovasculaire. Des &eacute;tudes ant&eacute;rieures r&eacute;v&egrave;lent que les &eacute;missions de l&#39;essence peuvent induire plusieurs voies enzymatiques impliqu&eacute;s dans la formation et le d&eacute;veloppement des plaques d&#39;ath&eacute;roscl&eacute;rose. Une comparaison directe, la pr&eacute;sente &eacute;tude a examin&eacute; l&#39;incidence des &eacute;missions de moteur diesel sur ces voies et examin&eacute;es plus en d&eacute;tail les effets sur la pathologie de la l&eacute;sion vasculaire. Souris apolipoprot&eacute;ine E-nulles &eacute;taient simultan&eacute;ment plac&eacute;es sur un r&eacute;gime riche en graisses et expos&eacute;s &agrave; des concentrations de quatre, plus une exposition forte concentration avec les particules (PM), &eacute;limin&eacute; par filtration, des &eacute;missions de diesel pour 6 h/jour pendant 50 jours. Aortes ont &eacute;t&eacute; dos&eacute;s par la suite pour les alt&eacute;rations matrix metalloproteinase-9, l&#39;endoth&eacute;line-1 et plusieurs autres biomarqueurs. Diesel provoquent des modifications li&eacute;es &agrave; la dose de marqueurs g&eacute;n&eacute;tiques du remodelage vasculaire et la peroxydation des lipides aortique ; filtration des particules n&#39;alt&eacute;ra pas significativement ces r&eacute;ponses vasculaires, indiquant que la partie gazeuse de l&#39;&eacute;chappement &eacute;tait un conducteur principal. Analyse immunohistochimique des sections d&eacute;pliant aortique a r&eacute;v&eacute;l&eacute; aucune augmentation nette de la zone de la l&eacute;sion, mais une baisse importante dans les r&eacute;gions riches en lipides et tendance &agrave; la hausse dans le contenu de l&#39;accumulation et le collag&egrave;ne macrophage, sugg&eacute;rant que les plaques ont &eacute;t&eacute; avanc&eacute;es &agrave; un &eacute;tat plus fragile et potentiellement plus vuln&eacute;rable par exposition aux gaz d&#39;&eacute;chappement de diesel. Combin&eacute;es avec des &eacute;tudes ant&eacute;rieures, ces r&eacute;sultats indiquent que toute &eacute;missions provenant de sources mobiles pourraient avoir un r&ocirc;le important dans la promotion d&#39;une maladie vasculaire chronique.

&Eacute;missions diesel inhal&eacute; modifient la composition de la plaque d&#39;ath&eacute;roscl&eacute;rose chez les souris ApoE(-/-).

Recenti studi epidemiologici suggeriscono che l&#39;inquinamento atmosferico di traffico possa avere effetti dannosi sulla salute cardiovascolare. Precedenti studi rivelano che le emissioni benzina possono indurre diversi percorsi di enzima coinvolti nella formazione e sviluppo di placche aterosclerotiche. Come un confronto diretto, il presente studio ha esaminato l&#39;impatto delle emissioni dei motori diesel su questi percorsi e ulteriormente esaminato gli effetti sulla patologia vascolare della lesione. Apolipoprotein E null topi simultaneamente erano collocati su una dieta high-fat chow ed esposto a concentrazioni di quattro, pi&ugrave; un&#39;esposizione ad alta concentrazione con particolato (PM) rimosso tramite filtrazione delle emissioni diesel per 6 ore al giorno per 50 giorni. Aortas sono stati successivamente analizzati per alterazioni in matrix metalloproteinase-9, endotelina-1 e diversi altri biomarcatori. Diesel indotta da alterazioni dose-correlata in marcatori di gene di rimodellamento vascolare e di perossidazione lipidica aortica; filtrazione di PM non alterano in modo significativo questi risposte vascolari, che indica che la parte gassosa del gas di scarico &egrave; stato un pilota principale. L&#39;analisi di immunohistochemical delle sezioni opuscolo aortica ha rivelato alcun aumento netto nella zona di lesione, ma una diminuzione significativa in regioni ricche di lipidi e crescenti tendenze in macrofago accumulo e collagene contenuto, suggerendo che placche erano avanzati a uno stato pi&ugrave; fragile, potenzialmente pi&ugrave; vulnerabile da esposizione al gas di scarico diesel. Combinato con gli studi precedenti, questi risultati indicano che tutta emissioni da fonti mobili possono avere un ruolo significativo nel promuovere la malattia vascolare cronica.

Le emissioni diesel inalato alterano composizione della placca aterosclerotica nei topi ApoE(-/-).

Emerging evidence suggests that the systemic vasculature may be a target of inhaled pollutants of vehicular origin. We have identified several murine markers of vascular toxicity that appear sensitive to inhalation exposures to combustion emissions.

A comparison of vascular effects from complex and individual air pollutants indicates a role for monoxide gases and volatile hydrocarbons.

Des preuves nouvelles sugg&egrave;rent que le syst&egrave;me vasculaire syst&eacute;mique peut &ecirc;tre une cible de polluants inhal&eacute;s d&#39;origine v&eacute;hiculaire. Nous avons identifi&eacute; plusieurs marqueurs murins de toxicit&eacute; vasculaire qui apparaissent sensibles &agrave; l&#39;exposition par inhalation aux &eacute;missions de combustion.

Une comparaison des effets vasculaires de polluants atmosph&eacute;riques complexes et individuel indique un r&ocirc;le pour gaz monoxyde et hydrocarbures volatils.

Prove emergenti suggerisce che il sistema vascolare sistemico pu&ograve; essere un bersaglio delle sostanze inquinanti inalati di origine veicolare. Abbiamo individuato diversi marcatori murini di tossicit&agrave; vascolare che appaiono sensibili alle esposizioni di inalazione alle emissioni di combustione.

Un confronto degli effetti vascolari da complessi e singoli inquinanti indica un ruolo per monossido gas e idrocarburi volatili.

Epidemiological studies have associated traffic-related airborne pollution with adverse cardiovascular outcomes. Nitric oxide (NO) is a common component of fresh diesel and gasoline engine emissions that rapidly transforms both in the atmosphere and once inhaled. Because of this rapid transformation, limited information is available in terms of potential human exposures and adverse health effects. Young rats were exposed to whole diesel emissions (DE) adjusted to 300 Î¼g/m(3) of particulate matter (containing 3.5 ppm NO) or 0, 3, or 10 ppm NO as a positive control. Animals were also pre-injected (ip) with either saline or N-acetylcysteine (NAC), a precursor of glutathione. Predictably, pure NO exposures led to a concentration-dependent increase in plasma nitrates compared to controls, which lasted for roughly 4 h postexposure. Whole DE exposure for 1 h also led to a doubling of plasma NOx. NAC injection increased the levels of plasma nitrates and nitrites (NOx) in the DE exposure group. Inhibition of nitric oxide symthase (NOS) by N(G)-nitro-L-arginine (L-NNA) did not block the rise in plasma NOx, demonstrating that the increase was entirely due to exogenous sources. Both DE and pure NO exposures paradoxically led to elevated eNOS expression in aortic tissue. Furthermore, coronary arterioles from NO-exposed animals exhibited greater constriction to endothelin-1 compared to controls, consistent with a derangement of the NOS system. Thus, NO may be an important contributor to traffic-related cardiovascular morbidity, although further research is necessary for proper hazard identification.

Formation of vascular S-nitrosothiols and plasma nitrates/nitrites following inhalation of diesel emissions.

Des &eacute;tudes &eacute;pid&eacute;miologiques ont associ&eacute; des effets cardiovasculaires ind&eacute;sirables li&eacute;s au trafic de la pollution atmosph&eacute;rique. Oxyde nitrique (NO) est un composant commun des frais diesel et les &eacute;missions des moteurs essence qui transforme rapidement dans l&#39;atmosph&egrave;re et une fois inhal&eacute;es. En raison de cette transformation rapide, peu d&#39;information est disponible en termes de risques d&#39;exposition humaines et effets sur la sant&eacute;. Jeunes rats ont &eacute;t&eacute; expos&eacute;s &agrave; des &eacute;missions de diesel enti&egrave;re (DE) ajust&eacute;es &agrave; 300 &mu;g/m(3) de particules (contenant 3,5 ppm ne) ou 0, 3 ou 10 ppm ne comme t&eacute;moin positif. Animaux ont &eacute;t&eacute; &eacute;galement pre-injected (ip) avec soit du s&eacute;rum physiologique ou N-ac&eacute;tylcyst&eacute;ine (NAC), un pr&eacute;curseur du glutathion. Comme pr&eacute;vu, pure, aucune exposition a entra&icirc;n&eacute; une augmentation d&eacute;pendante de la concentration en nitrates de plasma par rapport aux t&eacute;moins, qui a dur&eacute; &agrave; peu pr&egrave;s apr&egrave;s l&#39;infection 4 h. Ensemble DE l&#39;exposition pendant 1 h a &eacute;galement conduit &agrave; un doublement du plasma NOx. Injection du CNA a augment&eacute; les niveaux de plasma nitrates et nitrites (NOx) dans le groupe de l&#39;exposition DE. L&#39;inhibition de l&#39;oxyde nitrique symthase (NOS) de N (G) - nitro - L-arginine (L-NNA) n&#39;a pas bloqu&eacute; l&#39;augmentation plasmatique NOx, ce qui d&eacute;montre que l&#39;augmentation &eacute;tait enti&egrave;rement imputable &agrave; des sources exog&egrave;nes. Tant DE et non pure expositions paradoxalement conduit &agrave; l&#39;expression d&#39;eNOS &eacute;lev&eacute;es dans le tissu aortique. En outre, art&eacute;rioles coronaires des animaux expos&eacute;s non expos&eacute;es plue constriction &agrave; l&#39;endoth&eacute;line-1 par rapport aux t&eacute;moins, conformes &agrave; un d&eacute;r&egrave;glement du syst&egrave;me NOS. Ainsi, ne peut &ecirc;tre un facteur important de morbidit&eacute; cardiovasculaire li&eacute;e &agrave; la circulation, bien que d&#39;autres recherches sont n&eacute;cessaires pour l&#39;identification des risques appropri&eacute;e.

Formation de S-nitrosothiols vasculaire et plasma nitrates/nitrites apr&egrave;s inhalation d&#39;&eacute;missions diesel.

Studi epidemiologici hanno associato inquinamento traffico aereo con esiti cardiovascolari avversi. L&#39;ossido nitrico (NO) &egrave; un comune componente delle emissioni dei motori benzina e diesel fresco che trasforma rapidamente sia nell&#39;atmosfera che una volta inalato. A causa di questa trasformazione rapida, informazione limitata &egrave; disponibile in termini di potenziali esposizioni umane ed effetti avversi sulla salute. Giovani ratti sono stati esposti alle emissioni diesel tutto (DE) regolate a 300 &mu;g/m(3) di particolato (contenente 3,5 ppm NO) 0, 3 o 10 ppm non come controllo positivo. Gli animali sono stati anche pre-injected (ip) con una soluzione salina o N-acetilcisteina (NAC), un precursore del glutatione. Com&#39;era prevedibile, puro NO esposizioni ha portato a un aumento di concentrazione-dipendente di nitrati al plasma rispetto ai controlli, che dur&ograve; per circa postexposure 4 h. Tutta DE esposizione per 1 h ha portato anche ad un raddoppio del plasma NOx. Iniezione di NAC ha aumentato i livelli di plasma nitrati e nitriti (NOx) del gruppo di esposizione DE. Inibizione della symthase di ossido nitrico (NOS) da N (G) - nitro - L-arginina (L-NNA) non bloccare l&#39;aumento nel plasma di NOx, dimostrando che l&#39;aumento &egrave; stato interamente a causa di fonti esogene. Sia DE e puro NO esposizioni paradossalmente ha portato a eNOS elevata espressione nel tessuto aortico. Inoltre, delle arteriole coronariche da animali esposti NO esposto costrizione maggiore rispetto ai controlli, coerenti con una dismutazione del sistema NOS endotelina-1. Cos&igrave;, non pu&ograve; essere un contributore importante alla morbilit&agrave; cardiovascolari correlati a traffico, anche se ulteriori ricerche &egrave; necessario per la corretta identificazione.

Formazione di S-nitrosothiols vascolare e plasma nitrati/nitriti, dopo inalazione delle emissioni diesel.

The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, the biological effects of nanoparticle inhalation are poorly understood. Rats were exposed to nanosized titanium dioxide aerosols (10 Î¼g lung burden); at 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. Nanoparticle exposure did not alter perivascular nerve stimulation (PVNS)-induced arteriolar constriction under normal conditions; however, adrenergic receptor inhibition revealed a more robust effect. Nanoparticle inhalation reduced arteriolar dilation in response to active hyperaemia (AH). In both PVNS and AH experiments, nitric oxide synthase (NOS) inhibition affected only controls. Whereas cyclooxygenase (COX) inhibition only attenuated AH-induced arteriolar dilation in nanoparticle-exposed animals. This group displayed an enhanced U46619 constriction and attenuated iloprost-induced dilation. Collectively, these studies indicate that nanoparticle exposure reduces microvascular NO bioavailability and alters COX-mediated vasoreactivity. Furthermore, the enhanced adrenergic receptor sensitivity suggests an augmented sympathetic responsiveness.

Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways.

L&#39;augmentation g&eacute;n&eacute;ralis&eacute;e de la production et l&#39;utilisation des nanomat&eacute;riaux a augment&eacute; le risque d&#39;exposition des nanoparticules ; Cependant, les effets biologiques des nanoparticules par inhalation sont mal compris. Des rats ont &eacute;t&eacute; expos&eacute;s aux a&eacute;rosols de taille nano dioxyde de titane (charge de poumons 10 &mu;g) ; en prophylaxie post-exposition de 24h, le muscle de spinotrapezius a &eacute;t&eacute; pr&eacute;par&eacute; pour la microscopie intravitale. Exposition de nanoparticules n&#39;a pas alt&eacute;r&eacute; la stimulation des nerfs p&eacute;rivasculaires (PVNS)-induite par une constriction art&eacute;riolaire dans des conditions normales ; Cependant, l&#39;inhibition des r&eacute;cepteurs adr&eacute;nergiques a r&eacute;v&eacute;l&eacute; un effet plus robuste. Inhalation de nanoparticules r&eacute;duit la dilatation art&eacute;riolaire en r&eacute;ponse &agrave; une hyper&eacute;mie active (AH). Dans les exp&eacute;riences de PVNS et de AH, inhibition de l&#39;oxyde nitrique synthase (NOS) affect&eacute; uniquement des contr&ocirc;les. Alors que l&#39;inhibition des cyclooxyg&eacute;nases (COX) att&eacute;nu&eacute;e seulement dilatation art&eacute;riolaire AH-induite chez les animaux expos&eacute;s de nanoparticules. Ce groupe affiche une renforc&eacute;e U46619 constriction et att&eacute;nu&eacute;e iloprost induite par la dilatation. Collectivement, ces &eacute;tudes indiquent que l&#39;exposition de nanoparticules r&eacute;duit microvasculaire non biodisponibilit&eacute; et alt&egrave;re la vasor&eacute;activit&eacute; induite par COX. En outre, la sensibilit&eacute; accrue des r&eacute;cepteurs adr&eacute;nergiques sugg&egrave;re une r&eacute;activit&eacute; sympathique augment&eacute;e.

Inhalation de nanoparticules modifie une vasor&eacute;activit&eacute; art&eacute;riolaire syst&eacute;mique par des voies sympathiques et induite par la cyclo-oxyg&eacute;nase.

Il diffuso aumento nella produzione e nell&#39;utilizzo dei nanomateriali &egrave; aumentato il potenziale per l&#39;esposizione alle nanoparticelle; Tuttavia, gli effetti biologici di inalazione delle nanoparticelle sono capiti male. Ratti erano esposti agli aerosol di biossido di titanio di dimensioni nanometriche (onere del polmone 10 &mu;g); a post-esposizione di 24 h, il muscolo spinotrapezius &egrave; stato preparato per microscopia intravital. L&#39;esposizione delle nanoparticelle non alterava perivascolare stimolazione nervosa (PVNS)-indotta da costrizione arteriolare in condizioni normali; Tuttavia, l&#39;inibizione del recettore adrenergico ha rivelato un effetto pi&ugrave; robusto. Inalazione delle nanoparticelle ridotta dilatazione arteriolare in risposta a iperemia attiva (AH). In esperimenti sia PVNS e AH, ossido nitrico sintasi (NOS) inibizione colpiti solo i controlli. Considerando che l&#39;inibizione cyclooxygenase (COX) attenuato solo dilatazione arteriolare AH-indotte negli animali esposti delle nanoparticelle. Questo gruppo visualizzato un&#39;avanzata U46619 costrizione e dilatazione indotta da iloprost attenuato. Collettivamente, questi studi indicano che l&#39;esposizione delle nanoparticelle riduce NO microvascolare biodisponibilit&agrave; e altera vasoreactivity COX-mediata. Inoltre, la sensibilit&agrave; del recettore adrenergico avanzata suggerisce un&#39;aumentata reattivit&agrave; simpatica.

Inalazione delle nanoparticelle altera vasoreactivity arteriolare sistemico attraverso percorsi simpatici e cyclooxygenase-mediata.

On peuvent consid&eacute;rer les particules x&eacute;nobiotiques dans deux genres : particules de pollution de l&#39;air et engineered nanoparticles. Les expositions de particules peuvent se produire dans l&#39;environnement de plus, le lieu de travail et nos maisons. La plupart des recherches dans ce domaine a, l&eacute;gitimement, ax&eacute; sur les r&eacute;sultats et les r&eacute;actions pulmonaires. &Eacute;tudes plus r&eacute;centes indiquent que les effets cardiovasculaires sont capables de les corr&eacute;ler avec &eacute;tablies donn&eacute;es &eacute;pid&eacute;miologiques de la mortalit&eacute; et la morbidit&eacute; suite &agrave; une exposition de particules. Tandis que la toxicologie cardiovasculaire pr&eacute;liminaire et g&eacute;n&eacute;rale a &eacute;t&eacute; d&eacute;finie, les m&eacute;canismes derri&egrave;re ces effets, en particulier au sein de la microcirculation, sont en grande partie inexplor&eacute;s. Le but de cet examen est donc plusieurs fois : tout d&#39;abord, un aper&ccedil;u historique sur les aspects toxicologiques de la recherche de la particule est pr&eacute;sent&eacute;. Deuxi&egrave;me, discutera les d&eacute;finitions essentielles, terminologie et techniques qui ne sont pas familiers pour le scientifique microvasculaire. Troisi&egrave;mement, les plus r&eacute;cents concepts et hypoth&egrave;ses de recherche cardiovasculaire de conduite dans ce domaine seront examin&eacute;s. Enfin, les orientations futures possibles pour le scientifique microvasculaire seront propos&eacute;es. Collectivement parlant, microvasculaire recherche dans le domaine de l&#39;exposition de particule repr&eacute;sente bien plus qu&#39;un &laquo; cr&eacute;neau &raquo;. La demande imm&eacute;diate d&#39;&eacute;tudes fondamentales, translationnelles et cliniques est riche et diversifi&eacute;e. Microvasculaires scientifiques &agrave; tous les stades de la carri&egrave;re sont fortement encourag&eacute;s &agrave; d&eacute;velopper leurs int&eacute;r&ecirc;ts de recherche afin d&#39;inclure des enqu&ecirc;tes associ&eacute;es &agrave; des expositions de particules.

Exposition de particule x&eacute;nobiotiques et points de terminaison microvasculaires : un appel aux armes.

Xenobiotic particles can be considered in two genres: air pollution particulate matter and engineered nanoparticles. Particle exposures can occur in the greater environment, the workplace, and our homes. The majority of research in this field has, justifiably, focused on pulmonary reactions and outcomes. More recent investigations indicate that cardiovascular effects are capable of correlating with established mortality and morbidity epidemiological data following particle exposures. While the preliminary and general cardiovascular toxicology has been defined, the mechanisms behind these effects, specifically within the microcirculation, are largely unexplored. Therefore, the purpose of this review is several fold: first, a historical background on toxicological aspects of particle research is presented. Second, essential definitions, terminology, and techniques that may be unfamiliar to the microvascular scientist will be discussed. Third, the most current concepts and hypotheses driving cardiovascular research in this field will be reviewed. Lastly, potential future directions for the microvascular scientist will be suggested. Collectively speaking, microvascular research in the particle exposure field represents far more than a "niche." The immediate demand for basic, translational, and clinical studies is high and diverse. Microvascular scientists at all career stages are strongly encouraged to expand their research interests to include investigations associated with particle exposures.

Xenobiotic particle exposure and microvascular endpoints: a call to arms.

Xenobiotici particelle possono essere considerati in due generi: il particolato inquinamento di aria e progettato le nanoparticelle. Le esposizioni della particella possono verificarsi in ambiente maggiore, sul posto di lavoro e nelle nostre case. La maggior parte della ricerca in questo campo &egrave;, giustamente, concentrata sui risultati e reazioni polmonari. Le indagini pi&ugrave; recenti indicano che gli effetti cardiovascolari sono in grado di correlare con stabiliti dati epidemiologici mortalit&agrave; e morbilit&agrave; dopo le esposizioni delle particelle. Mentre &egrave; stata definita la tossicologia cardiovascolare preliminare e generale, i meccanismi dietro questi effetti, in particolare all&#39;interno del microcircolo, sono in gran parte inesplorati. Pertanto, lo scopo di questa recensione &egrave; parecchie volte: in primo luogo, viene presentato un background storico sugli aspetti tossicologici di ricerca della particella. Secondo, saranno discusso essenziali definizioni, terminologia e tecniche che possono risultare poco chiari allo scienziato microvascolare. In terzo luogo, verranno esaminati i pi&ugrave; attuali concetti e ipotesi guida ricerca cardiovascolare in questo campo. Infine, verranno suggerite potenziali future direzioni per lo scienziato microvascolare. Collettivamente parla, microvascolare ricerca nel campo dell&#39;esposizione delle particelle rappresenta molto di pi&ugrave; di una &quot;nicchia&quot;. La domanda immediata per gli studi di base, traslazionale e clinici &egrave; elevata e diversificata. Gli scienziati Microvascolari in tutte le fasi di carriera sono fortemente incoraggiati ad espandere i propri interessi di ricerca per includere le indagini associate con le esposizioni delle particelle.

L&#39;esposizione delle particelle xenobiotici ed endpoint microvascolare: una chiamata alle armi.

Air pollution PM is associated with cardiovascular morbidity and mortality. In Appalachia, PM from mining may represent a health burden to this sensitive population that leads the nation in cardiovascular disease, among others. Cardiovascular consequences following inhalation of PM(MTM) are unclear, but must be identified to establish causal effects.

Air pollution particulate matter collected from an appalachian mountaintop mining site induces microvascular dysfunction.

Pollution air PM est associ&eacute;e &agrave; la mortalit&eacute; et la morbidit&eacute; cardiovasculaire. Dans Appalachia, PM de l&#39;exploitation mini&egrave;re peut-&ecirc;tre repr&eacute;senter une charge sanitaire &agrave; cette population sensible qui m&egrave;ne la nation dans les maladies cardiovasculaires, entre autres. Cons&eacute;quences cardiovasculaires apr&egrave;s inhalation de PM(MTM) ne sont pas claires, mais doivent &ecirc;tre identifi&eacute;s pour cr&eacute;er des effets de causalit&eacute;.

Pollution de l&#39;air particules provenant d&#39;un site minier de montagne des Appalaches induit une dysfonction microvasculaire.

Inquinamento atmosferico PM &egrave; associato con la mortalit&agrave; e morbilit&agrave; cardiovascolare. In Appalachia, PM da data mining pu&ograve; rappresentare un onere di salute di questa popolazione sensibile che conduce la nazione nella malattia cardiovascolare, tra gli altri. Conseguenze cardiovascolari dopo inalazione di PM(MTM) non sono chiare, ma devono essere identificate per stabilire gli effetti causali.

Article	Year
Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis. Toxicological sciences : an official journal of the Society of Toxicology\| PubMed ID: 17065432	2007
Fine oil combustion particle bioavailable constituents induce molecular profiles of oxidative stress, altered function, and cellular injury in cardiomyocytes. Journal of toxicology and environmental health. Part A\| PubMed ID: 17934955	2007
Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS. Toxicology and applied pharmacology\| PubMed ID: 18455212	2008
Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 19150882	2009
Impairment of coronary endothelial cell ET(B) receptor function after short-term inhalation exposure to whole diesel emissions. American journal of physiology. Regulatory, integrative and comparative physiology\| PubMed ID: 19535675	2009
Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-) mice. Toxicology and applied pharmacology\| PubMed ID: 19891982	2010
A comparison of vascular effects from complex and individual air pollutants indicates a role for monoxide gases and volatile hydrocarbons. Environmental health perspectives\| PubMed ID: 20197249	2010
Formation of vascular S-nitrosothiols and plasma nitrates/nitrites following inhalation of diesel emissions. Journal of toxicology and environmental health. Part A\| PubMed ID: 21598168	2011
Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways. Nanotoxicology\| PubMed ID: 21830860	2012
Xenobiotic particle exposure and microvascular endpoints: a call to arms. Microcirculation (New York, N.Y. : 1994)\| PubMed ID: 21951337	2012
Air pollution particulate matter collected from an appalachian mountaintop mining site induces microvascular dysfunction. Microcirculation (New York, N.Y. : 1994)\| PubMed ID: 22963349	2013

Travis L. Knuckles

Biography

JoVE Journal Publications

Other Publications