Regulator of G Protein Signaling Protein 6 (RGS6) Protects the Heart from Ischemic Injury

Background Regulator of G protein signaling (RGS) proteins are important modulators of cardiac function. We previously reported that disruption of interactions between RGS proteins and Gα i2 protects the heart from ischemic injury. However, the ability of specific members of the RGS protein family to influence cardiac sensitivity to ischemic injury has not been previously explored. The goal of the present study was to determine how genetic deletion of specific RGS proteins influences myocardial sensitivity to ischemic injury. Methods Hearts from RGS1 knockout (RGS1 ‐/‐ ), RGS2 ‐/‐ , RGS2 ‐/‐ RGS4 ‐/‐ double knockout, RGS5 ‐/‐ , and RGS6 ‐/‐ mice, and their respective wildtype ( +/+ ) littermates were subjected to 30 min ischemia and 2 hours reperfusion using the Langendorff isolated heart model. Infarct sizes were measured by triphenyltetrazolium chloride staining. Results RGS6 ‐/‐ hearts had significantly larger infarcts than RGS6 +/+ hearts (51 ± 2 % and 34 ± 5 % area at risk, respectively). Importantly, deletion of RGS1, RGS2, RGS4, or RGS5 had no effect on infarct size indicating that this effect was specific for RGS6. We also found that RGS6 expression was significantly decreased in ventricles (but not atria) of RGS6 +/+ hearts subjected to ischemia / reperfusion injury. Conclusion These data demonstrate that expression of RGS6 protects the heart from ischemic injury. Modulating RGS6 may provide a novel therapeutic approach for the treatment of ischemic heart disease.