Abstract 1016: Inhibition of Vasa Vasorum Neovascularization Prevents Vessel Wall Inflammation and Intimal Hyperplasia in Early Atherosclerosis
Objective: To investigate the role of vasa vasorum (VV) neovascularization in early coronary atherosclerosis in the pig model of hypercholesterolemia.
Background: VV neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange surface to the coronary vessel wall. Thus, it is conceivable that VV favor the entry of pro-inflammatory and pro-atherosclerotic cellular and non-cellular blood components into the coronary vessel wall. We therefore hypothesized that prevention of VV neovascularization inhibits vessel wall inflammation and subintimal hyperplasia in early atherosclerosis. Thalidomide is a potent anti-angiogenic agent currently used in diseases characterized by pathological neovascularization.
Methods: Female domestic swine, 3-months of age, were fed either normal diet (group N, n = 12) or high-cholesterol diet (group HC, n = 12) for 3 months. In each group six pigs were placed on 200mg Thalidomide daily for the entire diet period (groups N + Th, HC + TH). Hearts were perfused with Microfil and LADs scanned with micro-CT (20 μm cubic voxel size) to determine VV spatial density (#/mm2). Fresh frozen coronary tissue was used for Western Blotting (VEGF, NFkB, LOX-1, TNF-alpha). Intima-Media thickness was measured in Elastic van Gieson stained histology slides. High-sensitive CRP and TNF-alpha levels were determined in serum samples.
Results: The anti-angiogenic treatment with Thalidomide preserved VV spatial density and inhibited the expression of VEGF, NfkappaB, TNF-alpha and LOX-1 in the coronary vessel wall (Table⇓). Histological measurements revealed a significant reduction in intima-media thickness in the HC + Th group compared to HC alone. There was no statistical significant difference in the serum levels of hsCRP and TNF-alpha between the four groups (Table⇓).
Conclusions: The inhibition of VV neovascularization in early atherosclerosis prevents vessel wall inflammation and subintimal hyperplasia.