Growth differentiation factor 11 attenuates diabetic myocardial injury via the NO-sGC-cGMP signaling pathway

Diabetic cardiomyopathy is a common complication in patients with diabetes, and effective therapeutic strategies remain limited. Although growth differentiation factor 11 (GDF11) has been reported to exert protective effects in cardiovascular diseases, its precise mechanisms of action remain unclear. In this study, a streptozotocin combined with high-fat, high-glucose diet-induced Sprague–Dawley rat model of diabetes was established. Administration of AAV9-GDF11 markedly attenuated myocardial injury in diabetic rats compared with untreated diabetic controls. Consistently, exogenous GDF11 reduced high glucose-induced apoptosis in H9c2 cardiomyocytes. Mechanistically, GDF11 alleviated cardiomyocyte apoptosis via activation of the NO-sGC-cGMP signaling pathway. Furthermore, inhibition of this pathway with N5-(1-Iminoethyl)-L-ornithine(L-NIO) partially abolished the cardioprotective effects of GDF11. Collectively, these findings demonstrate that GDF11 mitigates diabetic myocardial injury through the NO-sGC-PKG pathway, providing a potential therapeutic target for the prevention and treatment of diabetic cardiomyopathy.