Possible roles of angiotensin II-forming enzymes, angiotensin converting enzyme and chymase-like enzyme, in the human aneurysmal aorta.
Aortic aneurysm is a chronic degenerative condition associated with atherosclerosis. Recent studies have revealed that angiotensin (Ang) II plays important roles in atherosclerosis. In this study, to investigate the relationship between aortic aneurysm and Ang II, we measured the activities of the angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase-like enzyme, in human aneurysmal and control aortae. Aneurysmal aortic specimens were obtained from 16 aneurysm patients and control aortic specimens were obtained from 16 patients who underwent coronary artery bypass surgery (8 patients in each group were administered ACE inhibitors). The ACE and chymase-like enzyme activities were determined using extracts from vascular tissues. Both the ACE and chymase-like enzyme activities in the aneurysmal aortae were significantly higher than those in the control aortae (p < 0.01). In the patients treated with ACE inhibitors, the ACE activity in the aneurysmal aortae tended to be low, but the chymase-like enzyme activity tended to be high. In the aneurysmal aortae, the chymase-like enzyme activity in the adventitia was significantly higher than that in the intimal or medial layers (p < 0.01), while differences in ACE activity were not observed. Our results suggest that increases in local Ang II formation induced by chymase-like enzymes may play important roles in the pathogenesis of aneurysmal formation.
Tsunemi
Koutaro
K
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
Takai
Shinji
S
Nishimoto
Masayoshi
M
Yuda
Atsushi
A
Hasegawa
Shigeto
S
Sawada
Yoshihide
Y
Fukumoto
Hitoshi
H
Sasaki
Shinjiro
S
Miyazaki
Mizuo
M
D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001011:Aorta / Q000201:enzymology; D001014:Aortic Aneurysm / Q000201:enzymology*; D053818:Chymases; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012016:Reference Values; D012697:Serine Endopeptidases / Q000378:metabolism*; D017539:Tunica Intima / Q000201:enzymology; D017540:Tunica Media / Q000201:enzymology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases