characterization-immune-cells-human-adipose-tissue-using-flow

Characterization of Immune Cells in Human Adipose Tissue by Using Flow Cytometry

Infiltration of immune cells in the subcutaneous and visceral adipose tissue (AT) deposits leads to a low-grade inflammation contributing to the ...

MUMC

&#x7EC6;&#x80DE;&#x56E0;&#x5B50;&#x5728;&#x7F3A;&#x8840;&#x6027;&#x635F;&#x4F24;&#x4E0E;&#x4FEE;&#x590D;&#x4E2D;&#x7684;&#x91CD;&#x8981;&#x4F5C;&#x7528;&#x3002;&#x4F46;&#x662F;&#xFF0C;&#x4E86;&#x89E3;&#x751A;&#x5C11;&#x5728;&#x5FC3;&#x8840;&#x7BA1;&#x75BE;&#x75C5;&#x9884;&#x540E;&#x7684;&#x5173;&#x7CFB;&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x7684;&#x76EE;&#x7684;&#x662F;&#x8C03;&#x67E5;&#x9884;&#x540E;&#x8D8B;&#x5316;&#x56E0;&#x5B50; CCL3/&#x6309;&#x63ED;&#x4FDD;&#x9669;&#x8BA1;&#x5212;-1&alpha;&#x3001; CCL5/RANTES &#x548C; CCL18/PARC &#x7684;&#x6025;&#x6027;&#x51A0;&#x8109;&#x7EFC;&#x5408;&#x5F81; (ACS) &#x60A3;&#x8005;&#x672A;&#x6765;&#x5FC3;&#x8840;&#x7BA1;&#x4E8B;&#x4EF6;&#x7684;&#x98CE;&#x9669;&#x7684;&#x91CD;&#x8981;&#x6027;&#x3002;CCL3/&#x6309;&#x63ED;&#x4FDD;&#x9669;&#x8BA1;&#x5212;-1&alpha;&#x3001; CCL5/RANTES &#x548C; CCL18/PARC &#x7684;&#x57FA;&#x7EBF;&#x6C34;&#x5E73;&#x786E;&#x5B9A;&#x4ECE;&#x574F; Nauheim ACS &#x4E8C;&#x6CE8;&#x518C;&#x8868; ACS &#x60A3;&#x8005; &#xFF08;n = 609)&#x3002;&#x5728;&#x4E0B;&#x9762;&#x7684; 200 &#x5929;&#xFF0C;&#x75C5;&#x4EBA;&#x8FDB;&#x884C;&#x76D1;&#x7763;&#x7684;&#x81F4;&#x547D;&#x548C;&#x975E;&#x81F4;&#x547D;&#x7684;&#x5FC3;&#x8840;&#x7BA1;&#x4E8B;&#x4EF6;&#x7684;&#x53D1;&#x751F;&#x3002;&#x5728;&#x540E;&#x7EED;&#x671F;&#x95F4;&#x6709;&#x5173;&#x8054;&#x7684;&#x81F4;&#x547D;&#x4E8B;&#x4EF6;&#x98CE;&#x9669;&#x589E;&#x52A0; CCL3/MIP1&alpha;&#x3001; CCL5/RANTES &#x548C; CCL18/PARC &#x6D53;&#x5EA6;&#x6700;&#x9AD8;&#x7684; tertile &#x60A3;&#x8005; (HR&#xFF1A; 2.19&#xFF0C;95 %ci&#xFF1A; 1.04 4.61 CCL3/MIP1&alpha;&#xFF0C;HR &#x7684;&#xFF1A; 3.45&#xFF0C;95 %ci&#xFF1A; 1.54 7.72 CCL5/RANTES &#x548C; HR&#xFF1A; 3.14&#xFF0C;95 %ci&#xFF1A; 1.33 7.46 &#x4E3A; CCL18/PARC&#xFF09;&#x3002;&#x8FD9;&#x79CD;&#x98CE;&#x9669;&#x662F;&#x6700;&#x9AD8;&#x7684;&#x60A3;&#x8005;&#x4E2D;&#x4E0A;&#x90E8;&#x7684; tertile &#x7684;&#x6240;&#x6709;&#x4E09;&#x4E2A;&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x6D53;&#x5EA6; (HR: 2.52&#xFF0C;95 %ci&#xFF1A; 1.11 5.65&#xFF09;&#x3002;&#x5DF2;&#x77E5;&#x7684;&#x98CE;&#x9669;&#x53D1;&#x751F;&#x5FC3;&#x8840;&#x7BA1;&#x4E8B;&#x4EF6;&#x7684;&#x9884;&#x6D4B;&#xFF0C;&#x4EE5;&#x53CA; CCL3/&#x6309;&#x63ED;&#x4FDD;&#x9669;&#x8BA1;&#x5212;-1&alpha;&#x3001; CCL5/RANTES &#x548C; CCL18/&#x5E15;&#x6D1B;&#x963F;&#x5C14;&#x6258;&#x7814;&#x7A76;&#x4E2D;&#x5FC3;&#x8054;&#x5408;&#x6539;&#x8FDB; c-&#x81F3;&#x7684;&#x7EDF;&#x8BA1;&#x4ECE; 0.74 0.81 (p = 0.007)&#x3002;&#x6700;&#x540E;&#xFF0C;CCL3/&#x6309;&#x63ED;&#x4FDD;&#x9669;&#x8BA1;&#x5212;-1&alpha;&#x3001; CCL5/RANTES &#x548C; CCL18/PARC &#x662F;&#x72EC;&#x7ACB;&#x4E0E; ACS &#x60A3;&#x8005;&#x77ED;&#x671F;&#x6B7B;&#x4EA1;&#x98CE;&#x9669;&#x76F8;&#x5173;&#x8054;&#x3002;&#x7ED3;&#x5408;&#x6240;&#x6709;&#x7684;&#x4E09;&#x4E2A;&#x6807;&#x5FD7;&#x8FDB;&#x4E00;&#x6B65;&#x589E;&#x52A0;&#x5176;&#x9884;&#x540E;&#x7684;&#x4EF7;&#x503C;&#x3002;

&#x8D8B;&#x5316;&#x56E0;&#x5B50; CCL3/MIP1&alpha;&#xFF0C;CCL5/RANTES &#x548C; CCL18/PARC &#x662F;&#x6025;&#x6027;&#x51A0;&#x8109;&#x7EFC;&#x5408;&#x5F81;&#x60A3;&#x8005;&#x77ED;&#x671F;&#x6B7B;&#x4EA1;&#x7387;&#x72EC;&#x7ACB;&#x98CE;&#x9669;&#x9884;&#x6D4B;&#x3002;

Cytokines play an important role in ischemic injury and repair. However, little is known about their prognostic value in cardiovascular disease. The aim of this study was to investigate the prognostic importance of chemokines CCL3/MIP-1Î±, CCL5/RANTES and CCL18/PARC for the risk of future cardiovascular events in patients with acute coronary syndromes (ACS). Baseline levels of CCL3/MIP-1Î±, CCL5/RANTES and CCL18/PARC were determined in ACS patients from the Bad Nauheim ACS II registry (nâ€Š=â€Š609). During the following 200 days, patients were monitored for the occurrence of fatal and non-fatal cardiovascular events. Patients with CCL3/MIP1Î±, CCL5/RANTES and CCL18/PARC concentrations in the highest tertile were associated with an increased risk of a fatal event during follow-up (HR: 2.19, 95%CI: 1.04-4.61 for CCL3/MIP1Î±, HR: 3.45, 95%CI: 1.54-7.72 for CCL5/RANTES and HR: 3.14, 95%CI: 1.33-7.46 for CCL18/PARC). This risk was highest for patients with all three biomarkers concentrations in the upper tertile (HR: 2.52, 95%CI: 1.11-5.65). Together with known risk predictors of cardiovascular events, CCL3/MIP-1Î±, CCL5/RANTES and CCL18/PARC combined improved the c-statistics from 0.74 to 0.81 (pâ€Š=â€Š0.007). In conclusion, CCL3/MIP-1Î±, CCL5/RANTES and CCL18/PARC are independently associated with the risk of short-term mortality in ACS patients. Combining all three biomarkers further increased their prognostic value.

Chemokines CCL3/MIP1Î±, CCL5/RANTES and CCL18/PARC are Independent Risk Predictors of Short-Term Mortality in Patients with Acute Coronary Syndromes.

Cytokines jouent un r&ocirc;le important dans la r&eacute;paration et la l&eacute;sion isch&eacute;mique. Cependant, on conna&icirc;t leur valeur pronostique dans la maladie cardiovasculaire. Le but de cette &eacute;tude &eacute;tait d&#39;&eacute;tudier l&#39;importance pronostique des chimiokines CCL3/MIP-1&alpha;, CCL5/RANTES et CCL18/PARC du risque de futures complications cardiovasculaires chez les patients atteints de syndrome coronarien aigu (SCA). Niveaux de r&eacute;f&eacute;rence des CCL3/MIP-1&alpha;, CCL5/RANTES et CCL18/PARC ont &eacute;t&eacute; d&eacute;termin&eacute;s chez ACS du registre de Bad Nauheim ACS II (n = 609). Pendant 200 jours suivants, les patients ont &eacute;t&eacute; suivis pour la survenue d&#39;&eacute;v&eacute;nements cardiovasculaires mortelles et non mortelles. Patients avec des concentrations CCL3/MIP1&alpha;, CCL5/RANTES et CCL18/PARC dans le tertile sup&eacute;rieur &eacute;taient associ&eacute;es &agrave; un risque accru d&#39;un &eacute;v&eacute;nement fatal au cours du suivi (HR: 2.19, IC &agrave; 95 %: 1.04-4,61 pour CCL3/MIP1&alpha;, HR: 3.45, IC &agrave; 95 %: 1,54-7.72 CCL5/RANTES et RH &agrave;: 3,14, IC &agrave; 95 %: 1.33-7,46 pour CCL18/PARC). Ce risque &eacute;tait plus &eacute;lev&eacute; chez les patients atteints de toutes les concentrations de trois biomarqueurs dans le tertile sup&eacute;rieur (HR: 2.52, IC &agrave; 95 %: 1,11-5.65). Ainsi que des pr&eacute;dicteurs du risque d&#39;&eacute;v&eacute;nements cardiovasculaires, CCL3/MIP-1&alpha;, CCL5/RANTES et CCL18/PARC combin&eacute; am&eacute;lior&eacute;e du c-statistiques de 0,74 &agrave; 0,81 (p = 0,007). En conclusion, CCL3/MIP-1&alpha;, CCL5/RANTES et CCL18/PARC sont associ&eacute;s de fa&ccedil;on ind&eacute;pendante le risque de mortalit&eacute; &agrave; court terme chez les patients de l&#39;ACS. Combinant tous les trois biomarqueurs a encore augment&eacute; leur valeur pronostique.

Chimiokines CCL3/MIP1&alpha;, CCL5/RANTES et CCL18/PARC sont ind&eacute;pendant risque pr&eacute;dicteurs de courte dur&eacute;e mortalit&eacute; chez les Patients atteints de Syndromes coronariens aigus.

Zytokine spielen eine wichtige Rolle bei isch&auml;mischen Sch&auml;digung und Reparatur. Jedoch ist wenig bekannt &uuml;ber ihre prognostische Wert bei Herz-Kreislauf-Krankheit. Ziel dieser Studie war die prognostische Bedeutung der Chemokine CCL3/MIP-1&alpha;, CCL5/RANTES und CCL18/PARC f&uuml;r das Risiko zuk&uuml;nftiger kardiovaskul&auml;rer Ereignisse bei Patienten mit akuter koronarer Syndrome (ACS) zu untersuchen. Grundlinie Niveaus CCL3/MIP-1&alpha;, CCL5/RANTES und CCL18/PARC waren bestimmt bei ACS-Patienten aus der Registrierung Bad Nauheim ACS II (n = 609). In den folgenden 200 Tagen wurden die Patienten nach dem Vorkommen der t&ouml;dlichen und nicht t&ouml;dlichen Herz-Kreislauf-Ereignisse &uuml;berwacht. Patienten mit CCL3/MIP1&alpha;, CCL5/RANTES und CCL18/PARC-Konzentrationen in der h&ouml;chsten Tertile waren verbunden mit einem erh&ouml;hten Risiko eines schwerwiegenden Ereignisses w&auml;hrend der Follow-up (HR: 2.19, 95 % CI: 1.04-4.61 f&uuml;r CCL3/MIP1&alpha;, HR: 3,45, 95 % CI: 1,54-7,72 f&uuml;r CCL5/RANTES und HR: 3,14, 95 % CI: 1.33-7,46 f&uuml;r CCL18/PARC). Dieses Risiko wurde bei Patienten mit allen drei Biomarker-Konzentrationen in den oberen Tertile am h&ouml;chsten (HR: 2,52, 95 % CI: 1.11-5,65). Zusammen mit bekannten Risiko Pr&auml;diktoren f&uuml;r kardiovaskul&auml;re Ereignisse, verbesserte CCL3/MIP-1&alpha;, CCL5/RANTES und CCL18/PARC kombiniert die c-Statistiken von 0,74 bis 0,81 (p = 0,007). Abschlie&szlig;end sind CCL3/MIP-1&alpha;, CCL5/RANTES und CCL18/PARC unabh&auml;ngig verbunden mit dem Risiko eines kurzfristigen Sterblichkeit bei ACS-Patienten. Kombination aller drei Biomarker stieg weiter ihre prognostischen Wert.

Chemokine CCL3/MIP1&alpha;, sind CCL5/RANTES und CCL18/PARC unabh&auml;ngige Risiko Pr&auml;diktoren der kurzfristigen Sterblichkeit bei Patienten mit akuter koronarer syndrome.

Citochine svolgono un ruolo importante nella riparazione e lesione ischemica. Tuttavia, poco si sa circa il loro valore prognostico nella malattia cardiovascolare. Lo scopo di questo studio era di indagare l&#39;importanza prognostica di chemochine CCL3/MIP-1&alpha;, CCL5/RANTES e CCL18/PARC per il rischio di futuri eventi cardiovascolari nei pazienti con sindromi coronariche acute (ACS). Livelli basali di CCL3/MIP-1&alpha;, CCL5/RANTES e CCL18/PARC sono stati determinati in pazienti ACS dal Registro di Bad Nauheim ACS II (n = 609). Durante i giorni seguenti 200, i pazienti sono stati monitorati per l&#39;occorrenza di eventi cardiovascolari fatali e non fatali. Pazienti con concentrazioni CCL3/MIP1&alpha;, CCL5/RANTES e CCL18/PARC nel tertile pi&ugrave; alto sono stati associati con un aumento del rischio di un evento fatale durante il follow-up (HR: 2.19, 95% CI: 1,04-4.61 per CCL3/MIP1&alpha;, HR: 3,45, 95% CI: 1,54-7,72 per CCL5/RANTES e HR: 3.14, 95% CI: 1.33-7.46 per CCL18/PARC). Questo rischio era pi&ugrave; alto per i pazienti con tutte le concentrazioni di tre biomarcatori nel tertile superiore (HR: 2,52, IC 95%: 1,11-5,65). Insieme a predittori noto rischio di eventi cardiovascolari, CCL3/MIP-1&alpha;, CCL5/RANTES e CCL18/PARC combinato migliorato c-statistiche da 0,74 a 0,81 (p = 0.007). In conclusione, CCL3/MIP-1&alpha;, CCL5/RANTES e CCL18/PARC sono indipendentemente associati con il rischio di mortalit&agrave; a breve termine in pazienti di ACS. Combinando tutti i tre biomarcatori incrementato ulteriormente il loro valore prognostico.

Chemochine CCL3/MIP1&alpha;, CCL5/RANTES e CCL18/PARC sono predittori di rischio indipendente di breve termine mortalit&agrave; nei pazienti con sindromi coronariche Acute.

&#x30B5;&#x30A4;&#x30C8;&#x30AB;&#x30A4;&#x30F3;&#x306F;&#x3001;&#x865A;&#x8840;&#x6027;&#x640D;&#x50B7;&#x3068;&#x4FEE;&#x5FA9;&#x306B;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x518D;&#x751F;&#x3057;&#x307E;&#x3059;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x307B;&#x3068;&#x3093;&#x3069;&#x5FC3;&#x8840;&#x7BA1;&#x75BE;&#x60A3;&#x306E;&#x4E88;&#x5F8C;&#x306B;&#x3064;&#x3044;&#x3066;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x305B;&#x3093;&#x3002;&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3; il-1 &alpha; CCL3/MIP&#x3001;CCL5/RANTES &#x304A;&#x3088;&#x3073; CCL18/&#x30D1;&#x30EB;&#x30AF;&#x6025;&#x6027;&#x51A0;&#x75C7;&#x5019;&#x7FA4; &#xFF08;ACS&#xFF09; &#x60A3;&#x8005;&#x306B;&#x304A;&#x3051;&#x308B;&#x5C06;&#x6765;&#x306E;&#x5FC3;&#x8840;&#x7BA1;&#x30A4;&#x30D9;&#x30F3;&#x30C8;&#x306E;&#x30EA;&#x30B9;&#x30AF;&#x306E;&#x305F;&#x3081;&#x306E;&#x4E88;&#x5F8C;&#x306E;&#x91CD;&#x8981;&#x6027;&#x3092;&#x8ABF;&#x67FB;&#x3057;&#x305F;.CCL3/MIP il-1 &alpha;&#x3001;CCL5/RANTES &#x304A;&#x3088;&#x3073; CCL18/PARC &#x306E;&#x30D9;&#x30FC;&#x30B9;&#x30E9;&#x30A4;&#x30F3; &#x30EC;&#x30D9;&#x30EB;&#x60AA;&#x3044;&#x30CA;&#x30A6;&#x30CF;&#x30A4;&#x30E0; ACS II &#x30EC;&#x30B8;&#x30B9;&#x30C8;&#x30EA;&#x304B;&#x3089; ACS &#x60A3;&#x8005;&#x3067;&#x6C7A;&#x5B9A;&#x3055;&#x308C;&#x305F; (n = 609&#xFF09;&#x3002;&#x6B21;&#x306E; 200 &#x65E5;&#x9593;&#x3001;&#x60A3;&#x8005;&#x306E;&#x81F4;&#x547D;&#x7684;&#x306A;&#x975E;&#x81F4;&#x547D;&#x7684;&#x306A;&#x5FC3;&#x8840;&#x7BA1;&#x30A4;&#x30D9;&#x30F3;&#x30C8;&#x306E;&#x767A;&#x751F;&#x3092;&#x76E3;&#x8996;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x6700;&#x9AD8;&#x306E; tertile &#x306E; CCL3/MIP1&alpha;&#x3001;CCL5/RANTES &#x3068; CCL18/&#x30D1;&#x30EB;&#x30AF;&#x6FC3;&#x5EA6;&#x60A3;&#x8005;&#x3055;&#x308C;&#x305F;&#x30D5;&#x30A9;&#x30ED;&#x30FC; &#x30A2;&#x30C3;&#x30D7;&#x4E2D;&#x306B;&#x81F4;&#x547D;&#x7684;&#x306A;&#x30A4;&#x30D9;&#x30F3;&#x30C8;&#x306E;&#x30EA;&#x30B9;&#x30AF;&#x5897;&#x52A0;&#x3068;&#x95A2;&#x9023; (HR: 2.19&#x3001;95 %ci: 1.04-4.61 CCL3/MIP1&alpha;&#x3001;HR &#x306E;&#x305F;&#x3081;: 3.45&#x3001;95 %ci: 1.54-7.72 CCL5/RANTES &#x304A;&#x3088;&#x3073; HR: 3.14&#x3001;95 %ci: 1.33-7.46 CCL18/&#x30D1;&#x30EB;&#x30AF;)&#x3002;&#x3053;&#x306E;&#x30EA;&#x30B9;&#x30AF;&#x306F;&#x3001;&#x60A3;&#x8005;&#x306E;&#x3059;&#x3079;&#x3066;&#x306E; 3 &#x3064;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x6FC3;&#x5EA6;&#x4E0A;&#x90E8;&#x306E; tertile &#x3067;&#x6700;&#x9AD8;&#x3067;&#x3057;&#x305F; (HR: 2.52&#x3001;95 %ci: 1.11 5.65)&#x3002;&#x5FC3;&#x8840;&#x7BA1;&#x30A4;&#x30D9;&#x30F3;&#x30C8;&#x306E;&#x65E2;&#x77E5;&#x306E;&#x30EA;&#x30B9;&#x30AF;&#x4E88;&#x6E2C;&#x3068;&#x5171;&#x306B;&#x3001;CCL3/MIP il-1 &alpha;&#x3001;CCL5/RANTES &#x304A;&#x3088;&#x3073; CCL18/&#x30D1;&#x30EB;&#x30AF;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x308B;&#x6539;&#x5584; 0.81 c &#x7D71;&#x8A08; 0.74 &#x304B;&#x3089; (p = 0.007&#xFF09;&#x3002;&#x7D50;&#x8AD6;&#x3068;&#x3057;&#x3066;&#x306F;&#x3001;CCL3/MIP il-1 &alpha;&#x3001;CCL5/RANTES &#x304A;&#x3088;&#x3073; CCL18/&#x30D1;&#x30EB;&#x30AF;&#x72EC;&#x7ACB;&#x3057;&#x3066; ACS &#x60A3;&#x8005;&#x306B;&#x304A;&#x3051;&#x308B;&#x77ED;&#x671F;&#x6B7B;&#x4EA1;&#x30EA;&#x30B9;&#x30AF;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3059;&#x3079;&#x3066;&#x306E; 3 &#x3064;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x3092;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x3066;&#x3055;&#x3089;&#x306B;&#x4E88;&#x5F8C;&#x3092;&#x5897;&#x52A0;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;

&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3; CCL3/MIP1&alpha;&#x3001;CCL5/RANTES &#x3068; CCL18/&#x30D1;&#x30EB;&#x30AF;&#x72EC;&#x7ACB;&#x3057;&#x305F;&#x30EA;&#x30B9;&#x30AF;&#x56E0;&#x5B50;&#x306E;&#x77ED;&#x671F;&#x60A3;&#x8005;&#x306E;&#x6B7B;&#x4EA1;&#x7387;&#x6025;&#x6027;&#x51A0;&#x75C7;&#x5019;&#x7FA4;&#x3067;&#x3059;&#x3002;

Cytokines &#xD5C8; &#xD608; &#xC131; &#xC0C1;&#xD574; &#xBC0F; &#xBCF5;&#xAD6C;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xD55C;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xC57D;&#xAC04;&#xC758; &#xC2EC;&#xD608; &#xAD00; &#xC9C8;&#xD658;&#xC758; &#xC804;&#xC870;&#xC758; &#xAC00;&#xCE58;&#xC5D0; &#xB300; &#xD55C; &#xC54C;&#xB824;&#xC838; &#xC788;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xC758; &#xBAA9;&#xD45C;&#xB294; &#xC804;&#xC870; chemokines CCL3/&#xC131;&#xB2A5; &#xCE21;&#xC815;-1&alpha;, CCL5/RANTES &#xBC0F; CCL18/PARC &#xAE09;&#xC131; &#xAD00;&#xC0C1;&#xB3D9;&#xB9E5; &#xC99D;&#xD6C4;&#xAD70; (ACS) &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xBBF8;&#xB798; &#xC2EC;&#xC7A5; &#xD608;&#xAD00; &#xC0AC;&#xAC74;&#xC758; &#xC704;&#xD5D8;&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694;&#xC131;&#xC744; &#xC870;&#xC0AC; &#xD588;&#xB2E4;. &#xB098;&#xC05C; &#xB098; &#xC6B0; &#xD5F4; ACS II &#xB808;&#xC9C0;&#xC2A4;&#xD2B8;&#xB9AC;&#xC5D0;&#xC11C; ACS &#xD658;&#xC790;&#xC5D0;&#xC11C; CCL3/&#xC131;&#xB2A5; &#xCE21;&#xC815;-1&alpha;, CCL5/RANTES CCL18/PARC&#xC758; &#xAE30;&#xC900;&#xC120; &#xC218;&#xC900; &#xACB0;&#xC815; (n = 609). &#xB2E4;&#xC74C; 200 &#xC77C; &#xB3D9;&#xC548; &#xD658;&#xC790;&#xB294; &#xCE58;&#xBA85;&#xC801; &#xBC0F; &#xBE44; &#xCE58;&#xBA85;&#xC801; &#xC2EC;&#xD608; &#xAD00; &#xC0AC;&#xAC74;&#xC758; &#xBC1C;&#xC0DD;&#xC5D0; &#xB300; &#xD55C; &#xAC10;&#xC2DC; &#xB418;&#xC5C8;&#xB2E4;. CCL3/MIP1&alpha;, CCL5/RANTES &#xBC0F; CCL18/PARC &#xB18D;&#xB3C4;&#xAC00; &#xAC00;&#xC7A5; &#xB192;&#xC740; tertile&#xC5D0; &#xD658;&#xC790; &#xD6C4;&#xC18D; &#xB3D9;&#xC548; &#xCE58;&#xBA85;&#xC801;&#xC778; &#xC774;&#xBCA4;&#xD2B8;&#xC758; &#xC704;&#xD5D8; &#xC99D;&#xAC00;&#xC640; &#xAD00;&#xB828; &#xB41C; (HR: 2.19, 95 %ci: 1.04-4.61 CCL3/MIP1&alpha;, HR&#xC5D0; &#xB300; &#xD55C;: 3.45, 95 %ci: CCL5/RANTES &#xBC0F; HR 1.54-772: 3.14, 95 %ci: 1.33-7.46 CCL18/PARC&#xC5D0; &#xB300; &#xD55C;). &#xC774; &#xB9AC;&#xC2A4;&#xD06C;&#xB294; &#xC0C1;&#xB2E8; tertile&#xC5D0;&#xC11C; &#xBAA8;&#xB4E0; &#xC138; &#xAC1C;&#xC758; &#xC0DD;&#xCCB4; &#xB18D;&#xB3C4; &#xAC00;&#xC9C4; &#xD658;&#xC790;&#xC5D0; &#xB300; &#xD55C; &#xCD5C;&#xACE0; (HR: 2.52, 95 %ci: 1.11 5.65). &#xC54C;&#xB824;&#xC9C4;&#xB41C; &#xC704;&#xD5D8; &#xC2EC;&#xC7A5; &#xD608;&#xAD00; &#xC0AC;&#xAC74;&#xC758; &#xC608;&#xC5B8;&#xC790;, &#xD568;&#xAED8; CCL3/&#xC131;&#xB2A5; &#xCE21;&#xC815;-1&alpha;, CCL5/RANTES &#xBC0F; CCL18/PARC &#xACB0;&#xD569; &#xD5A5;&#xC0C1; c-&#xD1B5;&#xACC4; 0.74&#xC5D0;&#xC11C; 0.81&#xC5D0; (p = 0.007). &#xB05D;&#xC73C;&#xB85C;, CCL3/&#xC131;&#xB2A5; &#xCE21;&#xC815;-1&alpha;, CCL5/RANTES &#xBC0F; CCL18/PARC&#xB294; ACS &#xD658;&#xC790;&#xC758; &#xB2E8;&#xAE30; &#xC0AC;&#xB9DD;&#xB960;&#xC758; &#xC704;&#xD5D8;&#xC774; &#xB3C5;&#xB9BD;&#xC801;&#xC73C;&#xB85C; &#xC5F0;&#xACB0; &#xB429;&#xB2C8;&#xB2E4;. &#xBAA8;&#xB4E0; 3 &#xAC1C;&#xC758; &#xC0DD;&#xCCB4; &#xACB0;&#xD569; &#xD558; &#xC5EC; &#xB354;&#xC6B1; &#xADF8;&#xB4E4;&#xC758; &#xC804;&#xC870; &#xAC12; &#xC99D;&#xAC00;.

Chemokines CCL3/MIP1&alpha;, CCL5/RANTES CCL18/PARC &#xB3C5;&#xB9BD;&#xC801;&#xC778; &#xC704;&#xD5D8; &#xC608;&#xC5B8;&#xC790;&#xC758; &#xB2E8;&#xAE30; &#xC0AC;&#xB9DD;&#xB960; &#xAE09;&#xC131; &#xAD00;&#xC0C1; &#xB3D9;&#xB9E5; &#xC99D;&#xD6C4;&#xAD70; &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

Las citoquinas juegan un papel importante en la lesi&oacute;n isqu&eacute;mica y reparaci&oacute;n. Sin embargo, poco se sabe sobre su valor pron&oacute;stico en la enfermedad cardiovascular. El objetivo de este estudio era investigar la importancia pron&oacute;stica de quimiocinas CCL3/MIP-1&alpha;, CCL5/RANTES y CCL18/PARC para el riesgo de futuros eventos cardiovasculares en pacientes con s&iacute;ndromes coronarios agudos (SCA). Se determinaron los niveles iniciales de CCL3/MIP-1&alpha;, CCL5/RANTES y CCL18/PARC en pacientes de ACS en el registro de Bad Nauheim ACS II (n = 609). Durante los siguientes d&iacute;as 200, los pacientes fueron supervisados para la ocurrencia de eventos cardiovasculares fatales y no fatales. Pacientes con concentraciones de CCL3/MIP1&alpha;, CCL5/RANTES y CCL18/PARC en el tertil m&aacute;s alto se asociaron con un mayor riesgo de un acontecimiento fatal durante el seguimiento (HR: 2.19, IC del 95%: 1.04-4,61 para CCL3/MIP1&alpha;, HR: 3.45, IC del 95%: 1,54-7,72 CCL5/RANTES y HR: 3.14, IC del 95%: 1.33-7,46 CCL18/Parc). Este riesgo fue mayor para los pacientes con todas las concentraciones de tres biomarcadores en el tertil superior (HR: 2.52, IC del 95%: 1.11-5,65). Junto con predictores de riesgo de eventos cardiovasculares, CCL3/MIP-1&alpha;, CCL5/RANTES y CCL18/PARC combinado mejoraron las c-estad&iacute;sticas de 0,74 a 0.81 (p = 0.007). En conclusi&oacute;n, CCL3/MIP-1&alpha;, CCL5/RANTES y CCL18/PARC son independientemente asociados con el riesgo de mortalidad a corto plazo en los pacientes de ACS. Combinar todos los tres biomarcadores aument&oacute; a&uacute;n m&aacute;s su valor pron&oacute;stico.

Quimiocinas CCL3/MIP1&alpha;, CCL5/RANTES y CCL18/PARC son independientes riesgo predictores de corto plazo mortalidad en pacientes con s&iacute;ndromes coronarios agudos.

Leukocyte chemotaxis is deemed instrumental in initiation and progression of atherosclerosis. It is mediated by G-protein-coupled receptors (e.g., CCR2 and CCR5), the activity of which is controlled by G-protein-coupled receptor kinases (GRKs). In this study, we analyzed the effect of hematopoietic deficiency of a potent regulator kinase of chemotaxis (GRK2) on atherogenesis. LDL receptor-deficient (LDLr(-/-)) mice with heterozygous hematopoietic GRK2 deficiency, generated by bone marrow transplantation (n=15), displayed a dramatic attenuation of plaque development, with 79% reduction in necrotic core and increased macrophage content. Circulating monocytes decreased and granulocytes increased in GRK2(+/-) chimeras, which could be attributed to diminished granulocyte colony-forming units in bone marrow. Collectively, these data pointed to myeloid cells as major mediators of the impaired atherogenic response in GRK2(+/-) chimeras. LDLr(-/-) mice with macrophage/granulocyte-specific GRK2 deficiency (LysM-Cre GRK2(flox/flox); n=8) failed to mimic the aforementioned phenotype, acquitting these cells as major responsible subsets for GRK2 deficiency-associated atheroprotection. To conclude, even partial hematopoietic GRK2 deficiency prevents atherosclerotic lesion progression beyond the fatty streak stage, identifying hematopoietic GRK2 as a potential target for intervention in atherosclerosis.

Hematopoietic G-protein-coupled receptor kinase 2 deficiency decreases atherosclerotic lesion formation in LDL receptor-knockout mice.

The CD40/CD40L dyad is deemed to play a central role in several inflammatory processes, including atherosclerosis. As CD40 is overexpressed in atherosclerotic lesions, it constitutes a promising candidate for targeted imaging approaches. Here we describe the design of a novel, selective peptide ligand for CD40 by phage display. A synthetic peptide corresponding with the phage insert NP31 displayed nanomolar affinity for CD40. Affinity was further enhanced by mutimeric presentation of NP31. An essential 11-mer peptide motif was identified by truncation and alanine scan studies. Enriched phage selectively bound human CD40 and homed to inflammatory joints in a murine model of rheumatoid arthritis. NP31 ablated VEGF and IL-6 transcriptional activation and partially inhibited IL-6 production by CD40L-activated endothelial cells. Notably, NP31 did not only alter the biodistribution profile of a streptavidin scaffold but also markedly increased accumulation of the carrier in atherosclerotic aortic lesions of aged ApoE(-/-) mice in a CD40-dependent manner. This potent and selective peptide ligand has potential for targeted imaging and drug delivery approaches in CD40-dependent inflammatory disorders such as atherosclerosis.

Identification of a novel CD40 ligand for targeted imaging of inflammatory plaques by phage display.

Rupture-prone atherosclerotic plaques are characterized by inflammation and a large necrotic core. Inflammation is linked to high metabolic activity. Advanced glycation endproducts (AGEs) and their major precursor methylglyoxal are formed during high metabolic activity and can have detrimental effects on cellular function and may induce cell death. Therefore, we investigated whether plaque AGEs are increased in human carotid rupture-prone plaques and are associated with plaque inflammation and necrotic core formation.

Higher levels of advanced glycation endproducts in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype.

Plasmacytoid dendritic cells in atherosclerosis: knocking at T-cell's door.

Staging lymphocyte presence in human atherosclerosis: a tale told by numbers.

Normalization of hypercholesterolaemia, inflammation, hyperglycaemia, and obesity are main desired targets to prevent cardiovascular clinical events. Here we present a novel regulator of cholesterol metabolism, which simultaneously impacts on glucose intolerance and inflammation.

Deficiency of the oxygen sensor prolyl hydroxylase 1 attenuates hypercholesterolaemia, atherosclerosis, and hyperglycaemia.

Immune cell accumulation in adipose tissue (AT) is associated with the development of AT inflammation, resulting in metabolic dysfunction. Circulating immune cell patterns may reflect immune cell accumulation in expanding AT. However, data linking human leukocytes in blood and AT is lacking. We investigated whether blood immune cell populations are associated with their counterparts in subcutaneous (scAT) or visceral AT (vAT). Flow cytometry was performed on blood, scAT and vAT from 16 lean and 29 obese men. Circulating natural killer (NK)-cells, classical monocytes and nonclassical monocytes were higher in obese individuals. vAT, but not scAT, of obese individuals contained more inflammatory CD11c"M1" macrophages and NK cells compared to lean individuals. Blood classical monocytes were associated with CD11cmacrophages in vAT but not scAT. This association was unrelated to expression of the adhesion molecules CD11b and CD11c or of the chemokine receptor CX3CR1 on these monocytes. Other AT immune cells were not associated with their respective counterparts in blood. Finally, CD11cmacrophages and CD4T-cells in vAT were associated with their counterparts in scAT. In conclusion, blood classical monocytes reflect CD11cmacrophages in vAT.

Circulating classical monocytes are associated with CD11cmacrophages in human visceral adipose tissue.

Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis.F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake ofF-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors.

Feasibility of in vivoF-florbetaben PET/MR imaging of human carotid amyloid-β.

Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bimor wild type bone marrow transplanted ldlrmice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bimtransplanted mice displayed splenomegaly and overt lymphocytosis. CD4and CD8T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bimmice. Bimmice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bimmice.

Leukocyte Bim deficiency does not impact atherogenesis in ldlrmice, despite a pronounced induction of autoimmune inflammation.

Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11cproinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development.

Erik A.L. Biessen

CARIM,
Department of Pathology

MUMC

Characterization of Immune Cells in Human Adipose Tissue by Using Flow Cytometry

Erik A.L. Biessen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}CARIM,Department of Pathology

MUMC

Characterization of Immune Cells in Human Adipose Tissue by Using Flow Cytometry

CARIM,
Department of Pathology