Mast cell chymase induces apoptosis of vascular smooth muscle cells.
In human coronary atheromas, the numbers of degranulated mast cells and of apoptotic smooth muscle cells (SMCs) are increased. Accordingly, the possibility exists that mast cells participate in the regulation of SMC apoptosis in the lesions. Mast cells isolated from the serosal cavities of rats were stimulated to release their secretory granules. The neutral protease chymase, present in the exocytosed granules, was found to induce apoptosis when added to rat aortic SMCs in culture. The chymase-induced apoptosis of SMCs was detected by flow cytometry, microscopic analysis of cellular morphology, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), and electrophoretic demonstration of DNA laddering. Chymase induced SMC apoptosis in a dose- and time- dependent manner, and its proteolytic activity was essential for the proapoptotic effect. In addition to rat chymase, recombinant human chymase was also found to induce apoptosis of human coronary artery SMCs in culture. These results suggest that mast cells may participate in the apoptotic regulation of SMCs in atherosclerotic lesions.
Leskinen
M
M
Wihuri Research Institute, Helsinki, Finland.
Wang
Y
Y
Leszczynski
D
D
Lindstedt
K A
KA
Kovanen
P T
PT
D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism* / Q000503:physiopathology; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D053818:Chymases; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D012697:Serine Endopeptidases; D053818:Chymases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053181:Caspase 8; D053453:Caspase 9