ACCUMULATION OF ACTIVATED MAST-CELLS IN THE SHOULDER REGION OF HUMAN CORONARY ATHEROMA, THE PREDILECTION SITE OF ATHEROMATOUS RUPTURE

Background Rupture in the shoulder region of a coronary atheroma is co nsidered to be a sequel to local extracellular matrix degradation in t his highly vulnerable site. Such degradation could be triggered by mas t cells, which are filled with neutral proteases and are present in co ronary atheromas. However, the distribution and phenotype of mast cell s within coronary atheromas have not been studied. Methods and Results Specimens of normal and atherosclerotic human coronary intima from 32 autopsy cases with ages ranging from 13 to 67 years were stained with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. Of the tryptase-containing mast cells, a variabl e proportion (average, 40%; range, 0% to 100%) also contained chymase. In the normal coronary intimas, mast cells amounted to 0.1% of all nu cleated cells. In the fatty streaks, this proportion was higher by 9-f old, and in the cap, core, and shoulder regions of atheromas by 5-, 5- , and 10-fold, respectively. Electron and light microscopic studies of mast cells in the shoulder region of atheromas revealed degranulation of mast cells, a sign of their activation, and moreover, that the pro portion of activated mast cells was much higher (85%) in this region t han in the normal intima (18%). Conclusions The far higher proportion (50-fold) of activated mast cells in the shoulder region of atheromas supports the hypothesis that mast cells, a cell type capable of trigge ring matrix degradation, actively participate in the destabilization a nd ensuing rupture of coronary atheromas and thus may trigger an acute coronary event.