Liver-artery interactions via the plasminogen-CD36 axis in macrophage foam cell formation: New evidence for the role of remote organ crosstalk in atherosclerosis

摘要

Atherosclerosis is an inflammatory vascular disorder. Population studies linked hypercholesterolemia with coronary risk several decades ago. In the 1990s, preclinical and clinical evidence on lowering low-density lipoprotein (LDL) established that cholesterol not only promotes atherogenesis but also triggers the onset of acute thrombotic complications. Hypercholesterolemia promotes endothelial cell activation, recruiting circulating monocytes into the arterial wall, where they differentiate into macrophages. These proinfiammatory phagocytes then become lipid-laden foam cells, a hallmark of atherosclerosis. Although the direct role of loaded lipids remains obscure, these activated macrophage foam cells (as gauged by the expression of high levels of proinfiammatory factors such as cytokines and chemokines) activate vascular smooth muscle cells (SMCs), endothelial cells, and neighboring macrophages and induce the infiltration of additional immune cells into the lesion, which amplifies the athero-genic milieu in arteries. Matrix-degrading enzymes released by foam cells, such as matrix metalloproteinases (MMPs), and thrombogenic factors (eg, tissue factor) may reduce the mechanical stability of atherosclerotic plaques and trigger acute thrombosis.