Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via regulation of local myocardial C3 activity.
C3 is common to all pathways of complement activation augmenting ischemia/reperfusion (I/R)-induced myocardial injury and cardiac dysfunction. Complement inhibition with the complement regulatory protein, C1 inhibitor (C1INH), obviously exerts cardioprotective effects. Here, we examine whether C1INH regulates C3 activity in the ischemic myocardial tissue. C1INH markedly suppressed C3 mRNA expression and protein synthesis in both a model of I/R-induced rat acute myocardial infarction (AMI) and the cultured rat H9c2 heart myocytes. At least, this regulation was at the transcriptional level in response to oxygen tension. In vitro, C3 deposition on, and binding to, the surface of rat myocardial cells were significantly blocked by C1INH treatment. C1INH could inhibit classical complement-mediated cell lysis via suppressing the biological activity of C3. Therefore, C1INH, in addition to inhibition of the systemic complement activation, prevents myocardial cell injury via a direct inhibitory role in the local myocardial C3 activity.
Fu
Jinrong
J
Department of Cardiology, Renmin Hospital, Wuhan University School of Medicine, Wuhan, Hubei, PR China.
Lin
Guosheng
G
Zeng
Bin
B
Wu
Zhiwei
Z
Wu
Yanxia
Y
Chu
Honggang
H
Qin
Gangjian
G
Liang
Gong
G
Li
Jinan
J
Gan
Xiang
X
Yu
Xiaolan
X
Li
Chunhua
C
Liu
Dongxu
D
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002645:Chickens; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D003174:Complement C1 Inactivator Proteins; D003176:Complement C3; D010100:Oxygen