Adeno‐Sh Beta Catenin Abolishes Ischemic Preconditioning Mediated Cardioprotection by Downregulation of its Target Genes VEGF, Bcl‐2 & Survivin In Rat Myocardial Ischemia Model

β‐catenin (β‐cat) is a downstream target of Glycogen Synthase Kinase‐3β (GSK‐3β) that plays a vital role in ischemic preconditioning (IP) mediated angiogenesis & cardioprotection. In the present study we investigated the mechanism of IP mediated cardioprotection through cytosolic β‐cat stabilization, nuclear translocation & activation of its target genes VEGF, Bcl‐2 & survivin. β‐cat expression was suppressed by intramyocardial injection of adenovirus associated sh‐RNA against β‐cat (Ad‐sh‐β‐cat, 4×10 8 pfu). Adeno‐LacZ was used as the control. The rats were assigned to four groups (1) Control‐IR (CIR) (2) Ad‐LacZ + IR (LIR) (3) Ad‐LacZ + IP (LIP) (4) Ad‐sh‐β‐cat + IP (sh‐β‐catIP). 72h after injection, isolated hearts were subjected to 30min of ischemia [I] & 2h of reperfusion [R] (IR). Designated hearts were subjected to IP (5min of I + 10min R, 4 cycles) before IR. Significant reduction in left ventricular functional recovery throughout reperfusion & increased infarct size were observed in sh‐β‐catIP compared to LIP. Real time PCR & RT‐PCR analysis showed significant downregulation of mRNA expression of VEGF, Bcl‐2 & survivin in sh‐β‐catIP compared to LIP. These findings indicated for the first time that silencing β‐cat abolished IP mediated cardioprotection, thereby validating that β‐cat activation & nuclear translocation is necessary for the IP mediated expression of VEGF, Bcl‐2 & survivin.