Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta

Locally formed angiotensin II (Ang II) and mast cells may participate in th e development of atherosclerosis. Chymase, which originates from mast cells , is the major Ang II-forming enzyme in the human heart and aorta in vitro. The aim of the present study was to investigate aortic Ang II-forming acti vity (AIIFA) and the histochemical localization of each Ang II-forming enzy me in the atheromatous human aorta. Specimens of normal (n=9), atherosclero tic (n=8), and aneurysmal (n=6) human aortas were obtained at autopsy or ca rdiovascular surgery from 23 subjects (16 men, 7 women). The total, angiote nsin-converting enzyme (ACE)-dependent, and chymase-dependent AIIFAs in aor tic specimens were determined. The histologic and cellular localization of chymase and ACE were determined by immunocytochemistry, Total AIIFA was sig nificantly higher in atherosclerotic and aneurysmal lesions than in normal aortas. Most of AIIFA in the human aorta in vitro was chymase-dependent in both normal (82%) and atherosclerotic aortas (90%). Immunocytochemical stai ning of the corresponding aortic sections with antichymase, antitryptase or anti-ACE antibodies showed that chymase-positive mast cells were located i n the tunica adventitia of normal and atheromatous aortas, whereas ACE-posi tive cells were localized in endothelial cells of normal aorta and in macro phages of atheromatous neointima. The density of chymase- and tryptase-posi tive mast cells in the atherosclerotic lesions was slightly but not signifi cantly higher than that in the normal aortas, and the number of activated m ast cells in the aneurysmal lesions (18%) was significantly higher than in atherosclerotic (5%) and normal (1%) aortas. Our results suggest that local Ang II formation is increased in atherosclerotic lesions and that chymase is primarily responsible for this increase. The histologic localization and potential roles of chymase in the development of atherosclerotic lesions a ppear to be different from those of ACE.