Increased spatial vasa vasorum density in the proximal LAD in hypercholesterolemia—Implications for vulnerable plaque-development

Objective Vasa vasorum (VV) neovascularization is associated with advanced and ruptured atherosclerotic lesions that occur predominantly within the proximal third of the LAD. To investigate further the possible role of VV spatial distribution in determining this predominantly proximal location of complex lesions we analyzed the changes in VV spatial densities along the LAD in early atherosclerosis. Methods and results Three-month-old, female domestic pigs were placed on normal (N; n = 6) or high-cholesterol (HC; n = 6) diet for 3 months. VV count, vascular-area-fraction (∑vasa vasorum areas/mm2 vessel wall area, i.e., flow capacity), and the endothelial-surface-fraction (∑vasa vasorum endothelial surfaces/mm3 vessel wall volume) were calculated in three equal thirds of the coronary artery from microcomputed-tomography images. In N animals, the proximal thirds tended to have a higher vascular-area-fraction (mean ± S.D., 1.4 ± 0.6 versus 0.9 ± 0.3 and 0.9 ± 0.2%; P = 0.1) and endothelial-surface-fraction (0.72 ± 0.29 versus 0.59 ± 0.22 and 0.53 ± 0.20 mm2/mm3; NS) than the mid and distal thirds with significantly higher VV counts (26 ± 12, 15 ± 8, 8 ± 5, P = 0.01). In HC animals, we observed significant VV neovascularization (3.3 ± 1.2 n/mm2 versus 6.8 ± 1.9 n/mm2, P < 0.01), with significantly higher VV counts (24 ± 3 and 14 ± 3 versus 6 ± 4; P < 0.001) as well as higher vascular-area- (1.4 ± 0.2 and 1.4 ± 0.2% versus 0.8 ± 0.2%; P < 0.001) and endothelial-surface-fractions (0.88 ± 0.14 and 0.90 ± 0.12 mm2/mm3 versus 0.56 ± 0.14 mm2/mm3; P = 0.001) within the proximal and middle thirds compared to the distal third. Conclusions VV neovascularization in early atherosclerosis leads to a proximally accentuated increase in flow-capacity and endothelial-exchange-surface, which may favour the predominant development of vulnerable atherosclerotic plaques in proximal portions of the LAD.