Development of Coronary Atherosclerosis in Swine with Severe Hypercholesterolemia: Lack of Influence of von Willebrand Factor or Acute Intimal Injury

The development of coronary atherosclerosis in response to acute intimal injury and severe hypercholesterolemia was studied in 18 swine, nine normal and nine with von Willebrand's disease, an inherited disorder affecting platelet-vessel wall interactions. The left anterior descending coronary artery was denuded of endothelium by balloon catheterization, while the circumflex and right coronary arteries served as nonballooned controls. All swine were maintained on a 2% cholesterol diet for 4 months. The extent of atherosclerotic involvement was evaluated from four indices: percent intimal area, percent luminal narrowing, ratio of intimal to medial area, and luminal form. No differences in coronary atherosclerosis were observed between phenotypes in either ballooned or nonballooned vessels, nor were there any differences between ballooned and nonballooned vessels within either phenotype (p > 0.05). The major variable affecting coronary atherosclerosis was serum cholesterol. There was a significant positive relationship between serum cholesterol concentration and the extent of intimal lesions (r = 0.62, p = 0.006) that was independent of plasma von Willebrand factor concentration. These findings suggest that severe hypercholesterolemia promotes the development of porcine coronary atherosclerosis through a mechanism(s) that is independent of acute intimal injury or von Willebrand factor-mediated platelet response to injury.

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