Anti-apoptotic role for C1 inhibitor in ischemia/reperfusion-induced myocardial cell injury

Jinrong Fu, Guosheng Lin*, Zhiwei Wu, Bin Ceng, Yanxia Wu, Gong Liang, Gangjian Qin, Jinan Li, Isaac Chiu, Dongxu Liu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Complement activation augments myocardial cell injury and apoptosis during ischemia/reperfusion (I/R), whereas complement system inhibition with C1 inhibitor (C1INH), a serine protease inhibitor, exerts markedly cardioprotective effects. Our recent data demonstrate that C1INH prevents vascular endothelial cell apoptosis and a "modified" form of the reactive center loop-cleaved, inactive C1INH (iC1INH) plays an anti-inflammatory role in endotoxin shock. The aim of this study was to determine whether C1INH protects against myocardial cell injury via an anti-apoptotic activity or anti-inflammatory effect. In a rat model of acute myocardial infarction (AMI) induced by I/R, administration of C1INH protected against cardiomyocytic apoptosis via normalization of ratio of the Bcl-2/Bax expression in the myocardial infarct area. C1INH improved parameters of cardiac function and hemodynamics and reduced myocardial infarct size (MIS). In addition, myocardial and blood myeloperoxidase (MPO) activity, a marker of neutrophil infiltration, was decreased by treatment of C1INH. In cultured H9c2 rat cardiomyocytic cells, C1INH blocked hypoxia/reoxygenation-induced apoptosis in the absence of sera associated with inhibition of cytochrome c translocation and suppression of caspase-3 activation. The proportion of Bcl-2/Bax expression induced by hypoxia/reoxygenation was reversed by C1INH. Importantly, iC1INH also revealed these similar effects, indicating that C1INH has a direct anti-apoptotic activity. Therefore, these studies support the hypothesis that C1INH, in addition to inhibition of activation of the complement and contact systems, improves outcome in I/R-mediated myocardial cell injury via an anti-apoptotic activity independent of serine protease inhibitory activity.

Original languageEnglish (US)
Pages (from-to)504-512
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Oct 20 2006


  • Apoptosis
  • C1 inhibitor
  • Complement
  • Hypoxia
  • Infarction
  • Ischemia
  • Myocytes
  • Reoxygenation
  • Reperfusion

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Anti-apoptotic role for C1 inhibitor in ischemia/reperfusion-induced myocardial cell injury'. Together they form a unique fingerprint.

Cite this