Chapter 30 - Mast Cells in Atherosclerotic Human Coronary Arteries: Implications for Coronary Fatty Streak Formation, Plaque Ulceration and Control of Local Haemostatic Balance

Abstract

Systematic studies on mast cells in human coronary atherosclerotic lesions have demonstrated that the numbers of these cells are increased both in the foam cell-rich early lesions (fatty streaks) and in the rupture-prone advanced lesions (atheromas, also called atherosclerotic plaques). Regarding the potential roles of mast cells in the foam cell rich early lesions, the experimental results obtained with rat serosal mast cells served to identify a tightly regulated mechanism by which the stimulated mast cells promote the formation of foam cells when co-cultured with rodent peritoneal macrophages or with rodent smooth muscle cells. Regarding the potential roles of mast cells in the fibrous caps in advanced atherosclerotic plaques, three fundamental observations were made in vitro. First the heparin proteoglycans released from the stimulated mast cells inhibit proliferation of smooth muscle cells, and the chymase released induces their apoptosis. Second, experiments in vitro have revealed that human mast cell chymase (and tryptase) can activate matrix-degrading metalloproteinases. Third, the mast cell-derived soluble heparin proteoglycans possess significant inhibitory capacity in platelet reactivity toward collagen. The conceptual framework for the possible functions of mast cells in atherogenesis presents a compilation of data obtained by immunohistochemical techniques in human autopsy samples and experimental data obtained from animal cell culture systems and from biochemical experiments.