BAY 11-7082, a nuclear factor-κB inhibitor, reduces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model

Int Heart J. 2010;51(5):348-53. doi: 10.1536/ihj.51.348.

Abstract

Despite development of therapeutic modalities, myocardial ischemia-reperfusion (I/R) injury remains an important cause of cardiac dysfunction. Multiple strategies exist experimentally, but few are clinically available. Nuclear factor kappa-B (NF-κB) is a key transcription factor in the inflammatory response and is implicated in I/R injury. We hypothesized that the NFκB inhibitor BAY 11-7082 (BAY) would decrease the extent of injury after myocardial I/R. Hypoxia-reoxygenation (H/R) was induced in rat neonatal cardiomyocytes with or without BAY pretreatment. NF-κB activation, vascular cell adhesion molecule (VCAM)-1, and monocyte chemoattractant protein (MCP)-1 were assayed by immunocytochemistry, Western blot or reverse transcriptase-polymerase chain reaction (RT-PCR). Sprague-Dawley rats (n = 7) were administered BAY (130 µg/kg) and I/R was induced by ligation of the left anterior descending artery (LAD) for 30 minutes followed by reperfusion. Infarct size was analyzed after 24 hours. At 2 weeks, echocardiography was performed to evaluate ventricular function and hearts were analyzed for fibrosis and apoptosis. BAY treatment inhibited NF-κB p65 activation, as well as VCAM-1 and MCP-1 expression induced by H/R in cardiomyocytes. Compared with control rats, BAY pretreated rats showed reduced infarct size. Echocardiograms demonstrated preserved systolic function as a fractional shortening in the BAY+I/R group (P < 0.05). Fibrosis was reduced in the BAY+I/R group (P < 0.05) and apoptosis was also reduced in the BAY+I/R group (P < 0.05).In the rat myocardial I/R injury model, BAY significantly reduced the infarct size, and preserved myocardial function. These data demonstrate that a currently available and well-tolerated inhibitor of NF-κB can decrease the risk of myocardial injury associated with I/R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cells, Cultured
  • Chemokine CCL2 / blood
  • Disease Models, Animal
  • Immunohistochemistry
  • Inflammation / prevention & control
  • Myocytes, Cardiac / drug effects
  • NF-kappa B / antagonists & inhibitors*
  • Nitriles / pharmacology*
  • Nitriles / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Sulfones / pharmacology*
  • Sulfones / therapeutic use

Substances

  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • Chemokine CCL2
  • NF-kappa B
  • Nitriles
  • Sulfones