Expression of inducible nitric oxide synthase and Fas/Fas ligand correlates with the incidence of apoptotic cell death in atheromatous plaques of human coronary arteries

It was recently reported that inducible nitric oxide synthase was expressed in advanced atheromatous plaques. So we investigated the effect of NO or p eroxynitrite reactive product of NO or O-2(-) released by iNOS induced in m acrophages or T lymphocytes on inflammatory cells in atheromatous plaques o f human coronary arteries by immunohistochemistry. We found that iNOS was e xpressed in T lymphocytes and macrophages in T lymphocytes and macrophages coexisted advanced atheromatous areas. Most of the smooth muscle cells are not coexisted with T lymphocytes. We could not find iNOS in those smooth mu scle cells. Only a small number of iNOS-positive smooth muscle cells were f ound close to T lymphocytes and macrophages. Markers for apoptotic cells in duced in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) showed that many apoptotic T lymphocytes and macrophages e xisted near iNOS induced cells. Fas and Fas ligand were expressed in almost same areas that iNOS was expressed, By double-label immunostaining. Fas wa s expressed in T lymphocytes but Fas ligand was expressed in macrophages an d in some T lymphocytes, These results suggest that NO from iNOS induces Fa s and Fas ligand-mediated apoptosis and associates with regression of ather osclerosis. On the other hand, nitrotyrosine was detected wider areas than iNOS. So peroxynitrite from iNOS damages cells and tissues widely and may a ssociate with progression of atherosclerosis. These results suggest an impo rtant role of NOS in mediating both regressive changes and progressives cha nge in atheromatous plaques. (C) 2000 Academic Press.