Quantitation and Visualization of Vasa Vasorum and Neointimal Development in Three Dimensions - High-resolution Microscopic Computed Tomography Analysis

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Citation
US Cardiology, 2007;4(1):58-9

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Vasa vasora are the blood supply of the artery itself, originating in the adventitia in response to the arterial wall’s nutritional requirements. The presence of a thicker tunica media or neointima requires the development of vasa vasorum to meet the metabolic demands of the arterial wall, since diffusion from the arterial lumen alone is insufficient. Over 40 years ago Wolinsky and Glagov demonstrated that arteries with a medial thickness exceeding 0.47mm required vasa vasorum for nutrition.1 Vasa vasora can be further categorized into first-order vasa, which run longitudinal to the vessel lumen, and second-order vasa, which originate from the first-order vasa and are circumferential around the artery.2
The vasa vasora are necessary to maintain normal vessel wall homeostasis and inadequate perfusion of the vessel wall as deficiencies in the vasa have been shown to lead to intimal hyperplasia.3 The initial hypothesis relating atherosclerosis to increased development of the vasa vasorum was made by Barger et al. in 1984.4 Since then, it has been shown that coronary vasa neovascularization takes place early after induction of experimental hypercholesterolemia, suggesting a role for neovascularization in atherogenesis.5 This neovascularization has been shown to favor second-order vasa.2 Apolipoprotein E-deficient mice given the angiogenic factor vascular endothelial growth factor (VEGF), which leads to increased angiogenesis, show a subsequent increase in plaque area,6 while mice administered the anti-angiogenic factors endostatin and TNP-470 show decreased intimal hyperplasia.7 A decrease in intimal hyperplasia was also observed in a murine study following chronic endothelin receptor antagonism, which decreases VEGF expression and decreases vasa neovascularization.8 These studies provide evidence that neovascularization of the arterial wall is a crucial part of the atherosclerotic process. Abnormalities of the vasa vasorum have also been implicated in the development of neointimal hyperplasia after balloon angioplasty and stenting. In two animal models, local injury to the vascular wall stimulated intimal hyperplasia and adventitial neovascularization that was increased by VEGF and PR39 and tempered by the inhibition of VEGF and fibroblast growth factor, leading Khurana et al. to hypothesize that intimal hyperplasia has both angiogenesis-dependent and -independent phases.9 Indeed, it has previously been shown that following angioplasty injury, the number and density of adventitial microvessels increase in the initial three post-procedural days, then regress.10 Kwon et al. evaluated the spatial pattern of neovascularization, showing that although the number and diameter of the vasa increased after injury, the total vascular area was lower in injured vessels than in control vessels.11

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