Abstract P008: Impact of Hydrogen Sulfide on the Epigenetics of Diabetic Cardiomyopathy.

Abstract

Although Diabetic cardiomyopathy results in enhanced risk for heart failure, epigenetic changes leading to diabetic heart failure are unclear. Hydrogen sulfide (H2S) has been implicated in the preservation of heart function owing to its anti-inflammatory and positive metabolic changes. In the current study, we investigated whether or not chronic H2S treatment (by giving NaHS) reverses diabetic cardiomyopathy using mouse model of type-1 diabetes: Akita mice. Regulators of mitochondrial biogenesis, calcium handling and molecules that regulate post-ischemic recovery were assayed by western blotting and Q-PCR. Further, we considered epigenetic modifications such as microRNA expression changes and DNA methylation alterations to understand the causes of diabetic heart failure with and without NaHS treatment for 30 days. Our data indicated that chronic H2S treatment significantly reduced the mitochondrial fission inducers: Drp-1 (24%) and Fis-1 (17%) in the Akita mouse hearts. Further, there was enhancement (10%) in the SERCA2a expression after NaHS treatment in the diabetic hearts. Also, there was significant decrease (16%) in TNF-1α protein expression in diabetic hearts after NaHS treatment. In addition, there was significantly increased expression of post-ischemic recovery regulators such as: Notch3 (157%), C-JUN (160%), PGC-1α (173%), HIF-2α (72%) , and NRF-1 (149%) after NaHS treatment. These results suggest that the chronic NaHS treatment ameliorates diabetic cardiomyopathy through decreasing mitochondrial fission and inflammation and enhancing Ca2+ handling; as well as mitigating epigenetic changes leading to enhanced post-ischemic recovery potential.