Abstract 16051: Hydrogen Sulfide Therapy Induces Mitochondrial Biogenesis in the Setting of Ischemic-Induced Heart Failure
Background: Therapeutic strategies aimed at increasing the levels of hydrogen sulfide (H2S) exert cytoprotective effects in various models of cardiac injury. Here, we sought to determine if H2S therapy could induce mitochondrial biogenesis in the setting of ischemic-induced heart failure.
Methods and Results: Heart failure was induced by subjecting mice to 60 min of myocardial ischemia (MI) followed by reperfusion (R) for 4 wks, at which time left ventricular (LV) dimensions and function were evaluated with echocardiography and hemodynamics. The mice received saline (Veh) or sodium sulfide (Na2S, 100 μ g/kg) at the time of R followed by daily intravenous injections for the first 7 days of R. After 4 wks of R both groups displayed significant LV dilation and severe cardiac dysfunction. However, treatment with Na2S significantly reduced the degree of dilation and improved LV ejection fraction (Panel A), contractility, and relaxation when compared to Veh treated animals. In separate studies, myocardial tissue was collected to evaluate the effects of H2S therapy on mitochondria. Measurement of the ratio of mitochondrial to nuclear DNA demonstrated that mitochondrial numbers decreased by 54 ± 6% in the Veh-treated hearts, whereas treatment with Na2S preserved mitochondrial numbers (Panel B). This preservation was consistent with a stimulation of mitochondrial biogenesis by Na2S as the mRNA expression of PGC1α was significantly increased after treatment. Further corroborating the ability of H2S to induce mitochondrial biogenesis, mice with a cardiac-restricted overexpression of the H2S-generating enzyme CGL displayed a 20% increase in mitochondrial to nuclear DNA ratio (Panel C), as well as significantly increased expression of sirtuin-1 and PGC1α. Citrate synthase and complex I activity were also significantly augmented compared to wildtype mice.
Conclusion: These data suggest that H2S therapy augments mitochondrial numbers during heart failure via biogenesis.
- © 2012 by American Heart Association, Inc.