Lipid lowering reduces proteolytic and prothrombotic potential in rabbit atheroma

Abstract

Thrombus formation at sites of atheromatous plaque disruption cause most acute coronary events such as myocardial infarction and unstable angina. Lesional macrophages and smooth muscle cells produce matrix metallo-proteinases (MMPs) and tissue factor (TF), the molecules likely contribute to plaque rupture and thrombus formation. Recent clinical studies have suggested that lipid lowering can reduce the incidence of acute coronary events. We have recently determined the effects of long-term dietary lipid lowering on atheroma of high-cholesterol-fed rabbits. Lipid lowering diminished macrophage accumulation, reduced expression and activity of MMPs, and increased interstitial collagen accumulation in rabbit atheroma. Expression and activity of TF in atheroma also substantially decreased during lipid lowering. Dietary lipid lowering also promoted accumulation of mature smooth muscle cells expressing less MMPs and TF in the plaque's fibrous cap. These results suggest potential mechanisms by which lipid lowering reduces acute coronary events in patients by decreasing proteolytic and prothrombotic activity within the atheroma.