Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia

被引:185
作者
Herrmann, J
Lerman, LO
Rodriguez-Porcel, M
Holmes, DR
Richardson, DM
Ritman, EL
Lerman, A
机构
[1] Mayo Clin Rochester, Div Cardiovasc Dis, Rochester, MN 55905 USA
[2] Mayo Clin Rochester, Div Hypertens, Rochester, MN 55905 USA
[3] Mayo Clin Rochester, Dept Physiol & Biophys, Rochester, MN 55905 USA
关键词
angiogenesis; atherosclerosis; cholesterol; coronary disease; endothelial function;
D O I
10.1016/S0008-6363(01)00347-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Methods: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (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 coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93 +/-6%) and Group 2 (89 +/-7%) but impaired in Group 3 (71 +/- 11%; P <0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88 +/-2.45 per-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 demonstrates 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 vasorum neovascularization in the initial stage of atherosclerotic vascular disease. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:762 / 766
页数:5
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