Angiogenesis in Vein Grafts Impact of the External Stent

Surgery, ipso facto, elicits MV damage. In turn, the efficacy of revascularization may be axiomatic in determining the outcome of surgical procedures. One clinical scenario in which many of these factors come into play is in coronary artery bypass graft surgery (CABG) using autologous saphenous vein. CABG involves the removal of the vein from the patient, which is then implanted by anastomosis into the aortic arch and then below an atherosclerotic lesion in the coronary artery, effectively "bypassing" the occlusion and restoring normal blood flow. However, as many as 50 percent of grafts fail within 10 years because of reocclusion. CABG disrupts the integrity of the microvascular supply of the saphenous vein (the vasa vasorum). The vasa vasorum supplies larger blood vessels with oxygen and nutrients and removes metabolites and carbon dioxide since large vessels cannot derive their oxygen and nutrient requirements from blood flowing through their own lumens. The loss of vasa vasorum coupled with a rapidly thickening vein graft creates an imbalance between oxygen supply and demand that results in graft hypoxia. Hypoxia promotes VSMC proliferation, procoagulant pathways, and the expression of adhesion molecules in vascular tissue, all components of vein graft thickening and atherogenesis. However, as was mentioned earlier, the formation of a neo-vasa vasorum is designed to counteract the pathological impact of hypoxia.

The importance of angiogenesis in vein graft disease is highlighted by the effect of an external cuff or stent on vein graft morphology and angiogenesis. In the pig, placement of a nonrestrictive, highly porous external stent around implanted saphenous vein grafts markedly inhibits graft thickening and neointima formation (Figure 3). These stented vein grafts were characterized by a distinct "neo-adventitia" and a microvasculature that extended into the media of the graft. In contrast, the adventitia of unstented vein grafts was dispersed and poorly organized.

It was noted that within 1 week there was an exudate in the gap between the stent and the graft that contained components of fibrinolysis and leukocytes (Figure 4). At 2 weeks after implantation, this graft-stent interface was completely filled with a semiopaque "gel" or exudate that was fibrin-rich. At 1 month this had organized into a well-defined structure comprising a dense population of fibrob-lasts and microvessels (or neo-vasa vasorum). It was proposed, therefore, that the central mechanism underlying the effect of the external stent was the promotion of angiogenesis by this exudate. Once angiogenesis has been triggered, other endogenous growth factors come into play in the process. These adventitial microvessels contain a high density of B subtypes of the endothelin-1 receptor. This is of particular interest since ETB receptor agonists have been reported to promote angiogenesis. There are high levels of NOS in the endothelium of neoadventitial microvessels of stented porcine vein graft. Since NO promotes the proliferation and migration of endothelial cells, it was suggested that these observations pointed to a role for NO in stent-induced angiogenesis.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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