Relative localization of angiotensin-converting enzyme, chymase and angiotensin II in human coronary atherosclerotic lesions

Background Studies using cell cultures and animal models have indicated an important role for angiotensin II in atherosclerosis, In humans, at least t wo major enzymes are involved in the conversion of angiotensin I to angiote nsin II: so-called angiotensin-converting enzyme (ACE) and chymase, Enhance d activation of chymase in atherosclerotic tissue homogenates has been repo rted in animal models, but its contribution to the generation of angiotensi n II has not been studied. Objective To clarify the localization of chymase and its pathophysiologic r ole in the formation of angiotensin II, using human coronary arteries. Design and methods Twenty-four coronary artery segments obtained from 14 au topsied patients were characterized histologically into the following categ ories: normal coronary arteries with diffuse intimal thickening, hypercellu lar lesions, atheromatous plaques and fibrosclerotic plaques. We compared t he cellular localization of chymase, ACE and angiotensin II expression usin g immunocytochemical techniques. Results Chymase was expressed only in the cytosole of mast cells in all seg ments. On the basis of the histologic study, the number of chymase-positive cells in the intima of atheromatous plaques was significantly higher than that in normal coronary arteries with diffuse intimal thickening. The expre ssion of angiotensin II in the intima was enhanced in hypercellular lesions and atheromatous plaques. Localization of angiotensin II in the intima was associated with that of ACE. Immunodouble staining did not show colocaliza tion of angiotensin II and chymase. Conclusions These results suggest an important role for the production of a ngiotensin II by ACE in the progression of atherosclerosis in human coronar y arteries. Enhanced expression of chymase appears not to be involved in an giotensin II production in the intima, J Hypertens 1999, 17:547-553 (C) Lip pincott Williams & Wilkins.