Mast Cells in Atherosclerotic Human Coronary Arteries: Implications for Coronary Fatty Streak Formation and Plaque Erosion or Rupture

Abstract

Atherosclerosis is a slowly progressing disease of the intima, the innermost arterial layer. Fatty streaks appear first, then atheromas or atherosclerotic plaques develop, and, finally, the fibrous cap of a plaque may erode or rupture, triggering thrombus formation. Data emerging from clinical, pathological, and experimental studies on atherogenesis have revived a paradigm, according to which atherosclerosis is an inflammatory disease.! The inflammatory cells, notably macrophages, T lymphocytes, and mast cells are key players in the production of local inflammation in an atherosclerotic lesion. Importantly, immunohistochemical observations of atherosclerotic lesions in human coronary arteries have revealed that these lesions contain not only more macrophages and more T lymphocytes, but also more mast cells than does the normal coronary intima. Most importantly, the fraction of degranulated mast cells in the lesions is increased. Biochemical and cell culture experiments with degranulated rat serosal mast cells have suggested several mechanisms which, if operative in vivo, would provide mechanisms explaining how mast cells could influence the development of coronary atherosclerosis in man. First, the heparin proteoglycans and the neutral protease chymase in exocytosed mast cell granules can induce the formation of foam cells, the hallmarks of fatty streak lesions. Second, granule heparin proteoglycans can inhibit the proliferation of cultured smooth muscle cells. Third, granule chymase can induce their apoptosis. Since smooth muscle cells produce collagen, thus providing tensile strength in the fibrous cap, their loss would weaken the cap and render it susceptible to rupture. Together, these experimental observations have identified diverse functions by which mast cells may affect the development of atherosclerosis.