INDUCTION OF CHYMASE THAT FORMS ANGIOTENSIN-II IN THE MONKEY ATHEROSCLEROTIC AORTA

Chymase shows a catalytic efficiency in the formation of angiotensin ( Ang) II, In the present study, the characterization and primary struct ure of monkey chymase were determined, and the pathophysiological role of chymase was investigated on the atherosclerotic monkey aorta, Monk ey chymase was purified from cheek pouch vascular tissue using heparin affinity and gel filtration columns, The enzyme rapidly converted Ang I to Ang II (K-m = 98 mu M, k(cat) = 6203/min) but did not degrade se veral peptide hormones such as Ang II, substance P, vasoactive intesti nal peptide and bradykinin, The primary structure, which was deduced f rom monkey chymase cDNA, showed a high homology to that of human chyma se (98%), The mRNA levels of the aorta chymase were significantly incr eased in the atherosclerotic aorta of monkeys fed a high-cholesterol d iet. These results indicate that monkey chymase has a highly specific Ang II-forming activity and may be related to the pathogenesis of athe rosclerosis. (C) 1997 Federation of European Biochemical Societies.