CHYMASE-CONTAINING MAST-CELLS IN HUMAN ARTERIAL INTIMA - IMPLICATIONSFOR ATHEROSCLEROTIC DISEASE

Many of the mast cells present in human atherosclerotic lesions contai n chymase. As the lesions progress to more severe forms, the number of such mast cells increases, and their activity (degree of degranulatio n) increases. Exocytosed heparin-bound chymase may be involved in the development of both early (fatty streaks) and late (thrombotic) athero sclerotic lesions. Experimental studies with rat serosal mast cells ha ve revealed that chymase can degrade the apolipoprotein B-100 componen t of low-density lipoprotein (LDL) particles and the apolipoprotein A component of high-density lipoprotein (HDL) particles. Both of these c hymase actions on apolipoproteins tend to increase the cholesterol con tent of macrophages and to convert them into the foam cells typical of early atherosclerotic lesions. In atheromatous plaques, the late athe rosclerotic lesions, the chymase-containing mast cells may render the plaques unstable and their caps susceptible to rupture when chymase ac tivates the interstitial procollagenase secreted by the macrophages in the plaque caps. Definition of the quantitative importance of chymase in the pathogenesis of atherosclerosis and its complications remains an exciting challenge for the future.