Inhibition of endothelin converting enzyme-1 activity or expression ameliorates angiotensin II-induced myocardial hypertrophy in cultured cardiomyocytes.
Angiotensin II (Ang II)-induced hypertrophy response in cultured cardiomyocytes is partially mediated by endothelin-1 (ET-1). Endothelin converting enzyme-1 (ECE-1) is the rate limiting enzyme in the process of ET-1 production. In this study, two peptides which have significant inhibitory effect to the activity of rat ECE-1 purified from stable rat ECE-1-expressed CHO lines, were selected from 13 big ET-1 analogues. We found that treatment of P8 or P9 reversed the increase of hypertrophy genetic markers and cell surface area in primary cultured neonatal rat cardiomyocytes stimulated by Ang II. Besides, depletion of ECE-1 by RNA interference also revealed similar results as P8 or P9 treatment. These results confirmed that ECE-1 plays a key role in regulating Ang II-induced hypertrophy response in cultured cardiomyocytes.
Wang
Zhaohe
Z
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Cao
Yingnan
Y
Shen
Xiaoyan
X
Bu
Xianzhang
X
Bao
Yingxia
Y
Le
Kang
K
Mei
Zhengrong
Z
Tang
Shu
S
Yu
Shanshan
S
Liu
Peiqing
P
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015153:Blotting, Western; D016466:CHO Cells; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D019332:Endothelin-1 / Q000737:chemistry / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000648:ultrastructure; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D034622:RNA Interference / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D010455:Peptides; D000804:Angiotensin II; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes