Arterial shear stress reduces eph-b4 expression in adult human veins.

Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells.

BACKGROUND: During vein graft adaptation to the arterial circulation, vascular endothelial growth factor (VEGF) A expression transiently increases before becoming downregulated; however, the role of VEGF-A in venous remodeling is not clear. In addition, although VEGF-A stimulates angiogenesis and determines arterial identity in nascent arterial endothelial cells (EC), the role of VEGF-A in regulating identity in adult venous EC is also not clear. MATERIALS AND METHODS: EC, wild type (EphB4+/+) or heterozygous knockout (EphB4+/-), were stimulated with VEGF-A (0-100 ng/mL) and examined with quantitative polymerase chain reaction and western blotting. RESULTS: VEGF-A (100 ng/mL) inhibited expression of EphB4 and stimulated expression of delta-like ligand 4 (dll4) but did not stimulate either notch or EphrinB2 expression in adult venous EC. Pretreatment with VEGF receptor 2-neutralizing antibody abolished VEGF-stimulated downregulation of EphB4 but not the upregulation of dll4. Pretreatment with PD98059 or wortmannin showed that VEGF-A downregulation of EphB4 and upregulation of dll4 are mitogen-activated protein kinase kinase and extracellular signal-regulated kinase dependent but phosphatidylinositol 3 kinase-Akt independent. Compared with VEGF-induced EphB4 downregulation and dll4 upregulation in control EC, reduced EphB4 signaling in EphB4+/- EC showed even further downregulation of EphB4 and upregulation of dll4. CONCLUSIONS: Despite the genetic programming of arterial and venous EC fate, VEGF-A can repress venous identity in adult venous EC without induction of arterial identity. These changes in adult EC in vitro recapitulate the changes in identity described during vein graft adaptation to the arterial environment in vivo.

Current usage and future directions for the bovine pericardial patch.

Bovine pericardium (BP) is widely used in surgery and is commonly used as a patch after arteriotomy in cardiovascular surgery. BP patches have several advantages compared with prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding, and possibly reduced rates of infection. These advantages of BP have led to its common use during carotid endarterectomy (CEA). However, long-term clinical results reported after CEA have suggested several issues that may be related to the patch, including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification, and thrombosis. These complications may diminish the long-term efficacy of CEA and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which BP heals after patch angioplasty may lead to next generation tissue-engineered patches.

Cell-based interventions for therapeutic angiogenesis: review of potential cell sources.

Alternative therapies are currently being developed to treat patients with chronic limb ischemia who are unable to be revascularized in order to avoid amputation. Cell-based therapy using mononuclear cells is gaining attention as many clinical trials are currently underway. We review cell differentiation along with the different potential cell sources for use in therapeutic angiogenesis.

Age-related neointimal hyperplasia is associated with monocyte infiltration after balloon angioplasty.

Carotid angioplasty is associated with adverse events in elderly patients; it is unclear whether this is related to an altered inflammatory axis. The carotid arteries of young (6 months) or aged (22-24 months) Fischer 344 rats were balloon injured. Aged rats had reduced lumen area (0.18 ± 0.03 vs 0.24 ± 0.01 mm(2), p = .02) and increased neointimal thickening (0.15 ± 0.04 vs 0.08 ± 0.03 mm(2), p = .006). Aged rats had increased circulating monocytes (96 ± 21 vs. 54 ± 7; p = .002) as well as increased numbers of monocytes at the post-angioplasty site. Aged rats had sustained monocyte chemotactic protein-1 expression after angioplasty but young rats did not. Aged arteries also exhibited defective vasorelaxation and abnormal eNOS localization. Aged (≥80 years) human patients with high-grade carotid stenosis had increased number of monocytes (9.1% ± 0.4%) compared with younger (65-80 years) patients (8.1% ± 0.3%, p = .013). Aged rats develop neointimal hyperplasia after carotid angioplasty with increased numbers of monocytes, and elderly humans with carotid stenosis have increased numbers of circulating monocytes. These preliminary results may suggest a role for monocytes in the response to carotid angioplasty.