Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia

Objective: Experimental hypercholesterolemia is associated with vasa vasoru m neovascularization, unknown to occur before or after initial lesion forma tion. Thus, this study was performed to determine the temporal course of ne ovascularization of coronary vasa vasorum in relation to endothelial dysfun ction, a hallmark of early atherosclerosis. Methods: Female domestic pigs w ere fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 we eks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronar y vasa vasorum were assessed by three-dimensional microscopic computed tomo graphy. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93 +/-6%) and Group 2 (89 +/-7%) but impaired in G roup 3 (71 +/- 11%; P <0.05 vs. Group 1 and 2). In contrast, density of cor onary vasa vasorum was significantly higher in both Group 2 (4.88 +/-2.45 p er-mm(2)) and Group 3 (4.50 +/-1.37 per-mm(2)) compared to Group 1 (2.97 +/ -1.37 per-mm(2); P <0.05 vs. Group 2 and 3). Conclusion: This study demonst rates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vas orum neovascularization in the initial stage of atherosclerotic vascular di sease. (C) 2001 Elsevier Science B.V. All rights reserved.