Neovascularization in Human Atherosclerosis

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Abstract
In the absence of disease, the vasa vasorum nurture the outer component of the vessel wall, and the intima is fed by oxygen diffusion from the lumen. As disease progresses, the intima thickens, and oxygen diffusion is impaired. As a result, vasa become the major source for nutrients to the vessel wall.1 The vasa vasorum structure consists of a network of small arteries and veins, as shown in Figure 1. In the coronary arteries, vasa originate from bifurcation segments of epicardial vessels; in the ascending aorta, vasa originate from coronary and brachiocephalic arteries; and in the descending thoracic aorta, vasa originate from intercostal, lumbar, and mesenteric arteries.1 Figure 1. A, Volume-rendered high-resolution, 3-dimensional micro-CT image of the descending aorta vasa vasorum. B and C, Corresponding histological cross sections demonstrate atherosclerotic lesions in the inferior vena cava (black arrow). D, Highlighted differentiated arterial (red) and venous (blue) vasa vasorum. Masson trichrome stain; bar=500 μm. Reproduced with permission from Langheinrich AC, Michniewicz A, Sedding DG, Walker G, Beighley PE, Rau WS, Bohle RM, Ritman EL. Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(−/−)/low-density lipoprotein(−/−) double knockout mice. Arterioscler Thromb Vasc Biol . 2006;26:347–352. Copyright 2006, American Heart Association. Sympathetic fibers help vasa to regulate blood flow, as shown in Figure 2. Vasa react to adenosine and endothelin-1.2,3 However, vasa appear to be relatively insensitive to thromboxane A2, norepinephrine, and angiotensin II, providing neuronal protection against ischemia during sustained sympathetic activity.3 The vasa vasorum are also sensitive to acetylcholine, histamine, isoprenaline, adenosine triphosphate, adenosine diphosphate, adenosine, and sodium nitroprusside.4 Additionally, precontracted vasa exhibit endothelium-dependent vasodilatation to bradykinin and substance P, which are mediated by endothelium-dependent hyperpolarization and nitric oxide, respectively.4 As a result, vasa response to some agonists …