Integrin-Linked Kinase Activation Prevents Ventricular Arrhythmias Induced by Ischemia/Reperfusion Via Inhibition of Connexin 43 Remodeling

Ischemia reperfusion (I/R)-induced arrhythmia is a serious complication in patients with cardiac infarction. Remodeling of connexin (Cx) 43, manifested as phosphorylation, contributes significantly to arrhythmogenesis. Integrin-linked kinase (ILK) attenuated ventricular remodeling and improved cardiac function in rats after myocardial infarction. We hypothesized that ILK, through Cx43 phosphorylation, would be protective against I/R-induced ventricular arrhythmias. Our study showed that I/R-induced ventricular arrhythmias were attenuated by an ILK agonist LPTP and worsened by the ILK inhibitor Cpd22. I/R disrupted Cx43 distribution, but it was partially normalized in the presence of LPTP. Compared with I/R, the phosphorylation of Akt was increased significantly after pretreatment with LPTP. The increase in phosphorylated Akt was physiologically significant because, in the presence of the Akt inhibitor MK2206, the protective effects of LPTP were blocked. This indicated that ILK activation prevented I/R-induced-ventricular arrhythmia, an effect potentially related to inhibition of Cx43 remodeling via Akt activation.

Automated summary

Ischemia reperfusion-induced ventricular arrhythmias can be regulated by ILK agonists and inhibitors, with ILK activation potentially preventing arrhythmias through Akt activation to inhibit Cx43 remodeling.