Segmental Heterogeneity of Vasa Vasorum Neovascularization in Human Coronary Atherosclerosis

Objectives Our aim was to investigate the role of coronary vasa vasorum (VV) neovascularization in the progression and complications of human coronary atherosclerotic plaques. Background Accumulating evidence supports an important role of VV neovascularization in atherogenesis and lesion location determination in coronary artery disease. VV neovascularization can lead to intraplaque hemorrhage, which has been identified as a promoter of plaque progression and complications like plaque rupture. We hypothesized that distinctive patterns of VV neovascularization and associated plaque complications can be found in different stages of human coronary atherosclerosis. Methods Hearts from 15 patients (age 52 ± 5 years, mean ± SEM) were obtained at autopsy, perfused with Microfil (Flow Tech, Inc., Carver, Massachusetts), and subsequently scanned with micro-computed tomography (CT). The 2-cm segments (n = 50) were histologically classified as either normal (n = 12), nonstenotic plaque ( 2 ), VV vascular area fraction (mm 2 /mm 2 ), and VV endothelial surface fraction (mm 2 /mm 3 ). Histological sections were stained for Mallory's (iron), von Kossa (calcium), and glycophorin-A (erythrocyte fragments) as well as endothelial nitric oxide synthase, vascular endothelial growth factor, and tumor necrosis factor-alpha. Results VV density was higher in segments with nonstenotic and noncalcified stenotic plaques as compared with normal segments (3.36 ± 0.45, 3.72 ± 1.03 vs. 1.16 ± 0.21, p Conclusions Our results support a possible role of VV neovascularization, VV rupture, and intraplaque hemorrhage in the progression and complications of human coronary atherosclerosis.