The Beta Subunit Of Soluble Guanylyl Cyclase Gucy1b3 Exerts Cardioprotective Effects Against Ischemic Injury Via The Pkc Epsilon/Akt Pathway

The soluble form of guanylyl cyclase (sGC) is the main receptor for the signaling agent nitric oxide (NO), which regulates cardiomyocyte contractile function and attenuates cardiomyocyte hypertrophy. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), a regulator of vascular tone, and cardiac NO-sGC-cGMP signaling modulates cardiac stress responses, including ischemia and reperfusion (IR) injury. Here, we investigated the role of GUCY1B3 (the beta subunit of sGC) in cardiomyocyte IR injury and myocardial infarction (MI) in vitro and in vivo. GUCY1B3 was upregulated in neonatal rat ventricular myocytes in response to IR injury, and GUCY1B3 overexpression restored IR-induced cell death and apoptosis. Treatment with specific inhibitors of PKC delta, PKC epsilon, and Akt suggested that the protective effects of GUCY1B3 were mediated by PKC epsilon/Akt signaling. In a mouse model of coronary artery ligation-induced MI, GUCY1B3 silencing aggravated MI-induced cardiac dysfunction and increased infarct size and exacerbated cardiomyocyte apoptosis in association with the inactivation of PKC epsilon and Akt. Our results suggest that GUCY1B3 exerts cardioprotective effects through the modulation of the PKC epsilon/Akt activity and identify a potential mechanism involved in NO-sGC-cGMP signaling in the heart.