The mast cell, a rich source of neutral proteases in atherosclerotic plaques

摘要

Mast cells, an inflammatory cell type highly enriched in intracellular granules containing the neutral proteases, tryptase and chymase, are present in both early and late human coronary atherosclerotic lesions.Our in vitro studies have suggested that activated mast cells promote the conversion of both macrophages and smooth muscle cells (SMCs) into foam cells.In this conversion, the key process is proteolytic modification of low-density lipoproteins (DDL) and high-density lipoprbteins (HDL), the former accelerating the cellular influx of cholesterol and the latter preventing the cellular efflux of cholesterol.In addition to effects related to lipid metabolism and foam cell formation, novel functions for mast cells in ather'othrombosis are emerging. Experimental studies have shown that chymase and heparin proteoglycans secreted by activated mast cells may destabilize the plaque by inhibiting SMC proliferation and collagen synthesis, and by activating latent interstitial collagenase (MMP-1) Furthermore, by degrading fibronectin with subsequent loss of outside-in survival signaling, chymase induces SMC apoptosis in vitro. Activated mast cells can also induce apoptosis of endothelial cells (ECs) by a mechanism partly involving secretion of tumor necrosis factor-alpha (TNF-alpha).These recent findings suggest a role for mast cells both in early and late stages of atherosclerosis.