patch-angioplasty-in-the-rat-aorta-or-inferior-vena-cava

Patch Angioplasty in the Rat Aorta or Inferior Vena Cava

Pericardial patches are commonly used in vascular surgery to close vessels. To facilitate studies of the neointimal hyperplasia that forms on the patch, ...

murine-model-central-venous-stenosis-using-aortocaval-fistula-with-an

Murine Model of Central Venous Stenosis using Aortocaval Fistula with an Outflow Stenosis

Central venous stenosis is an important entity contributing to arteriovenous fistula (AVF) failure. A murine AVF model was modified to create a partial ...

Yale University

VA Connecticut Healthcare Systems, West Haven, CT

The clinical characteristics and long-term results of patients with solitary iliac aneurysms (SIAs) were investigated.

Treatment of solitary iliac aneurysms: clinical review of 28 cases.

The role of testosterone in atherosclerosis remains unclear because it is aromatized to estrogen. We investigated the effect of the nonaromatized natural androgen 5alpha-dihydrotestosterone (DHT) on the rabbit atherogenesis in relation to the proatherogenic molecule lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1) and its downstream molecules. Thirty-nine male New Zealand white rabbits were divided into four groups: 1) noncastrated group with normal chow diet (n = 6); 2) noncastrated group with high-cholesterol diet (HCD) (n = 10); 3) castrated group with HCD plus sc placebo pellet (n = 11); and 4) castrated group with HCD plus sc 150 mg DHT pellet (n = 12). Implantation of sc DHT or placebo pellet was performed at the time of castration. After castration or sham operation, the rabbits were fed the HCD for 8 wk, and plaque areas were assessed in the entire aorta. The HCD-induced increase in plaque area, which was most aggravated in the castration plus placebo group, was attenuated in the castration plus DHT group. Microscopic examination of the proximal descending aorta revealed that DHT significantly reduced HCD-induced foam cell formation, which was mostly composed of macrophages in the intima layer, compared with the placebo group. The decreased accumulation of foam cells with DHT treatment was accompanied by a marked reduction in the expression of LOX-1 mRNA in these cells. In cultured macrophages prepared from male wild-type mice that express the androgen receptor (AR), 1 x 10(-8) m and 1 x 10(-9) m DHT inhibited the formation of foam cells induced by oxidized low-density lipoprotein. Moreover, the expression of LOX-1 and inflammatory cytokines in the cultured macrophages was significantly suppressed by DHT. Such suppressive effects of DHT on foam cell formation and cytokine expression were not observed in cultured macrophages prepared from male AR-null mice, suggesting an involvement of AR in the mechanism. In conclusion, physiological levels of DHT attenuated the development of atherosclerosis in rabbits through the suppression of intimal foam cell formation of macrophage partly via the suppression of LOX-1 expression.

Dihydrotestosterone suppresses foam cell formation and attenuates atherosclerosis development.

Our experience with unilateral iliac reconstructive surgery was retrospectively reviewed, and the long-term patency and the morphological information was disclosed. In addition, the prognosis of contralateral iliac artery was examined, because future contralateral iliac events seem to be important for durability of unilateral iliac revascularizations.

Long-term Results of Reconstructive Surgery for the Unilateral Aortoiliac Occlusive Disease and Future Risks of Contralateral Iliac Events.

Homocysteine (Hcy) has been implicated in abdominal aortic aneurysm (AAA). However, the association of Hcy, vitamin B12, and folate in patients with AAA has not been studied in China. This study was conducted with the aim to evaluate the relationship of vitamin B12, folic acid, and Hcy levels in AAA.

Hyperhomocysteinaemia, low folate concentrations and MTHFR C677T mutation in abdominal aortic aneurysm.

Phlegmasia cerulea dolens is a rare condition caused by complete venous occlusion leading to impaired arterial flow. To prevent progression to limb gangrene, prompt diagnosis and treatment initiation are paramount. Here we report a rare case of posttraumatic phlegmasia cerulea dolens after ligation of the iliac vein to save the patient's life, with successful treatment by reconstructing the external iliac vein. This is the first report of posttraumatic phlegmasia cerulea dolens induced by iliac vein ligation.

Successful treatment of posttraumatic phlegmasia cerulea dolens by reconstructing the external iliac vein: a case report.

Vascular diseases span diverse pathology, but frequently arise from aberrant signaling attributed to specific membrane-associated molecules, particularly the Eph-ephrin family. Originally recognized as markers of embryonic vessel identity, Eph receptors and their membrane-associated ligands, ephrins, are now known to have a range of vital functions in vascular physiology. Interactions of Ephs with ephrins at cell-to-cell interfaces promote a variety of cellular responses such as repulsion, adhesion, attraction, and migration, and frequently occur during organ development, including vessel formation. Elaborate coordination of Eph- and ephrin-related signaling among different cell populations is required for proper formation of the embryonic vessel network. There is growing evidence supporting the idea that Eph and ephrin proteins also have postnatal interactions with a number of other membrane-associated signal transduction pathways, coordinating translation of environmental signals into cells. This article provides an overview of membrane-bound signaling mechanisms that define vascular identity in both the embryo and the adult, focusing on Eph- and ephrin-related signaling. We also discuss the role and clinical significance of this signaling system in normal organ development, neoplasms, and vascular pathologies.

Membrane-mediated regulation of vascular identity.

Pericardial patches are commonly used during cardiovascular surgery to close blood vessels. In arteries, patches accumulate arterial progenitor cells; we hypothesized that venous patches would accumulate venous progenitor cells, in the absence of arterial pressure. We developed a novel rat inferior vena cava (IVC) venotomy model and repaired it with a pericardial patch. Cells infiltrated the patch to form a thick neointima by day 7; some cells were CD34(+)/VEGFR2(+) and CD31(+)/Eph-B4(+) consistent with development of venous identity in the healing patch. Compared to arterial patches, the venous patches had increased neointimal thickness at day 7 without any pseudoaneurysms. Addition of an arteriovenous fistula (AVF) to increase blood flow on the patch resulted in reduced patch neointimal thickness and proliferation, but neointimal thickness was not reversible with AVF ligation. These results show that rat patch venoplasty is a novel model of aggressive venous neointimal hyperplasia.

Pericardial patch venoplasty heals via attraction of venous progenitor cells.

Arteriovenous fistulae (AVF) remain the optimal conduit for hemodialysis access but continue to demonstrate poor patency and poor rates of maturation. We hypothesized that CD44, a widely expressed cellular adhesion molecule that serves as a major receptor for extracellular matrix components, promotes wall thickening and extracellular matrix deposition during AVF maturation.

CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation.

With the increasing prevalence of end-stage renal disease, there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis, but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes in the setting of uremia, systemic inflammation, oxidative stress, and pre-existent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis and development of neointimal hyperplasia that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to neointimal hyperplasia involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure require a multidisciplinary approach involving nephrologists, vascular surgeons, and interventional radiologists, careful patient selection, and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy.

Future research directions to improve fistula maturation and reduce access failure.

Polyester is commonly used in vascular surgery for patch angioplasty and grafts. We hypothesized that polyester patches heal by infiltration of arterial or venous progenitor cells depending on the site of implantation. Polyester patches were implanted into the Wistar rat aorta or inferior vena cava and explanted on day 7 or 30. Neointima that formed on polyester patches was thicker in the venous environment compared to the amount that formed on patches in the arterial environment. Venous patches had more cell proliferation and greater numbers of VCAM-positive and CD68-positive cells, whereas arterial patches had greater numbers of vimentin-positive and alpha-actin-positive cells. Although there were similar numbers of endothelial progenitor cells in the neointimal endothelium, cells in the arterial patch were Ephrin-B2- and notch-4-positive while those in the venous patch were Eph-B4- and COUP-TFII-positive. Venous patches treated with an arteriovenous fistula had decreased neointimal thickness; neointimal endothelial cells expressed Ephrin-B2 and notch-4 in addition to Eph-B4 and COUP-TFII. Polyester patches in the venous environment acquire venous identity, whereas patches in the arterial environment acquire arterial identity; patches in the fistula environment acquire dual arterial-venous identity. These data suggest that synthetic patches heal by acquisition of identity of their environment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3422-3431, 2017.

Polyester vascular patches acquire arterial or venous identity depending on their environment.

Autogenous vein grafts remain the gold standard conduit for arterial bypass, particularly for the treatment of critical limb ischemia. Vein graft adaptation to the arterial environment, i.e., adequate dilation and wall thickening, contributes to the superior performance of vein grafts. However, abnormal venous wall remodeling with excessive neointimal hyperplasia commonly causes vein graft failure. Since the PREVENT trials failed to improve vein graft outcomes, new strategies focus on the adaptive response of the venous endothelial cells to the post-surgical arterial environment. Eph-B4, the determinant of venous endothelium during embryonic development, remains expressed and functional in adult venous tissue. After surgery, vein grafts lose their venous identity, with loss of Eph-B4 expression; however, arterial identity is not gained, consistent with loss of all vessel identity. In mouse vein grafts, stimulation of venous Eph-B4 signaling promotes retention of venous identity in endothelial cells and is associated with vein graft walls that are not thickened. Eph-B4 regulates downstream signaling pathways of relevance to vascular biology, including caveolin-1, Akt, and endothelial nitric oxide synthase (eNOS). Regulation of the Eph-B4 signaling pathway may be a novel therapeutic target to prevent vein graft failure.

Improving the Outcome of Vein Grafts: Should Vascular Surgeons Turn Veins into Arteries?

Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-β (transforming growth factor-β) signaling plays a mechanistic role in the development of pseudoaneurysms.

Transforming Growth Factor-β1 Inhibits Pseudoaneurysm Formation After Aortic Patch Angioplasty.

Penetrating aortic ulcer (PAU) is an acute aortic syndrome that can proceed to life-threatening aortic dissection or even aortic rupture. Isolated iliac aneurysms are relatively rare and often asymptomatic due to their deep pelvic location but are frequently associated with high mortality with rupture. We report a case of a 68-year-old man with a symptomatic penetrating ulcer in the descending aorta and an asymptomatic right iliac aneurysm involving the common and internal iliac arteries. The patient was successfully treated by endovascular repair in a single-stage manner using stent grafts in the descending aorta and right common iliac artery after coil embolization of the right internal iliac artery. Follow-up imaging showed complete resolution of the PAU and exclusion of the right iliac aneurysm without endoleak. Aggressive endovascular treatment for a symptomatic PAU with an asymptomatic isolated iliac aneurysm is feasible and allows complete treatment of vascular pathology at a single time.

Single-stage Endovascular Treatment of a Penetrating Aortic Ulcer with a Concomitant "Isolated" Iliac Aneurysm.

Diabetic foot ulcer (DFU) is a severe complication of diabetes, preceding most diabetes-related amputations. DFUs require over US$9 billion for yearly treatment and are now a global public health issue. DFU occurs in the setting of ischemia, infection, neuropathy, and metabolic disorders that result in poor wound healing and poor treatment options. Recently, stem cell therapy has emerged as a new interventional strategy to treat DFU and appears to be safe and effective in both preclinical and clinical trials. However, variability in the stem cell type and origin, route and protocol for administration, and concomitant use of angioplasty confound easy interpretation and generalization of the results.

Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research.

Arteries, veins, and lymphatic vessels are distinguished by structural differences that correspond to their different functions. Each of these vessels is also defined by specific molecular markers that persist throughout adult life; these markers are some of the molecular determinants that control the differentiation of embryonic undifferentiated cells into arteries, veins, or lymphatics.

Molecular identity of arteries, veins, and lymphatics.

Androgen receptor (AR) signaling is involved in the initiation and progression of prostate cancer (PCa), which is the most frequently diagnosed nonskin cancer and remains a leading cause of cancer-related death in men. Further investigation of the involvement of AR signaling in PCa progression is urgently needed. In the present study, we performed a yeast two-hybrid screen and demonstrated that SERTA domain-containing protein 1 (Sertad1) is a novel AR-binding protein that binds to the AR ligand binding domain (LBD). The binding between AR-LBD and Sertad1 was confirmed by glutathione S-transferase (GST) pull-down assays and immunoprecipitation (IP) and confocal immunofluorescence co-localization experiments. Furthermore, we demonstrated that DHT inhibited Sertad1 protein degradation in prostate cancer cell lines and that Sertad1 knockdown inhibited the proliferation of prostate cancer cells in vitro. In human PCa tumor tissues, Sertad1 expression is positively correlated with AR expression and the Gleason score. Taken together, this report is the first to show that Sertad1 is a novel AR-LBD-binding protein, and DHT-liganded AR-LBD inhibits Sertad1 degradation. Thus, Sertad1 may represent a novel therapeutic target for the treatment of AR-positive PCa.

Sertad1 promotes prostate cancer progression through binding androgen receptor ligand binding domain.

Vascular smooth muscle cells (SMCs) synthesize extracellular matrix (ECM) that contributes to tissue remodeling after revascularization interventions. The cytokine transforming growth factor β (TGF-β) is induced on tissue injury and regulates tissue remodeling and wound healing, but dysregulated signaling results in excess ECM deposition and fibrosis. The LIM (Lin11, Isl-1 & Mec-3) domain protein LIM domain only 7 (LMO7) is a TGF-β1 target gene in hepatoma cells, but its role in vascular physiology and fibrosis is unknown.

ArticleTotal : 2	Year
Publication title	2017
Publication title	2019

Article	Year
Treatment of solitary iliac aneurysms: clinical review of 28 cases. Surgery today\| PubMed ID: 18306997	2008
Dihydrotestosterone suppresses foam cell formation and attenuates atherosclerosis development. Endocrinology\| PubMed ID: 20427482	2010
Long-term Results of Reconstructive Surgery for the Unilateral Aortoiliac Occlusive Disease and Future Risks of Contralateral Iliac Events. Annals of vascular diseases\| PubMed ID: 23555389	2010
Hyperhomocysteinaemia, low folate concentrations and MTHFR C677T mutation in abdominal aortic aneurysm. VASA. Zeitschrift fur Gefasskrankheiten\| PubMed ID: 24797049	2014
Successful treatment of posttraumatic phlegmasia cerulea dolens by reconstructing the external iliac vein: a case report. Journal of medical case reports\| PubMed ID: 24885801	2014
Membrane-mediated regulation of vascular identity. Birth defects research. Part C, Embryo today : reviews\| PubMed ID: 26992081	2016
Pericardial patch venoplasty heals via attraction of venous progenitor cells. Physiological reports\| PubMed ID: 27354544	2016
CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 28450292	2017
Future research directions to improve fistula maturation and reduce access failure. Seminars in vascular surgery\| PubMed ID: 28779782	2016
Polyester vascular patches acquire arterial or venous identity depending on their environment. Journal of biomedical materials research. Part A\| PubMed ID: 28877393	2017
Improving the Outcome of Vein Grafts: Should Vascular Surgeons Turn Veins into Arteries? Annals of vascular diseases\| PubMed ID: 29034014	2017
Transforming Growth Factor-β1 Inhibits Pseudoaneurysm Formation After Aortic Patch Angioplasty. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 29146747	2018
Single-stage Endovascular Treatment of a Penetrating Aortic Ulcer with a Concomitant "Isolated" Iliac Aneurysm. Aorta (Stamford, Conn.)\| PubMed ID: 29766010	2017
Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research. Stem cell research & therapy\| PubMed ID: 29996912	2018
Molecular identity of arteries, veins, and lymphatics. Journal of vascular surgery\| PubMed ID: 30154011	2019
Sertad1 promotes prostate cancer progression through binding androgen receptor ligand binding domain. International journal of cancer\| PubMed ID: 30230528	2019
LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis. Circulation\| PubMed ID: 30586711	2019

Haidi Hu

Biography

JoVE Journal Publications

Other Publications