Protective effects and mechanisms of hydrogen sulfide on isoproterenol-induced cardiac hypertrophy in mice

[Speaker] Guoliang Meng:1
[Co-author] Yun Chen:1, Shengju Yang:1,2, Mengting Xu:1, Wei Zhang:1
1:School of Pharmacy, Nantong University, China, 2:Affiliated Hospital of Nantong University, China

Background Hydrogen sulfide (H2S) is a gasotransmitter with a variety of cardiovascular protective effects. Sirtuin 3 (sirtuin 3, SIRT3) is closely related to mitochondrial function and oxidative stress. The aim of this study was to investigate whether H2S improved the cardiac hypertrophy induced by isoproterenol (ISO) in a SIRT3 dependent manner and to explore possible mechanisms. Methods 12 week old male 129S1/SvImJ (WT) mice and SIRT3 deficiency mice were intraperitoneally injected with normal saline or NaHS for two weeks and then intraperitoneally injectied with ISO for another two weeks. At the end of the administration, the cardiac index, the cross-sectional area of the cardiomyocytes, the expression of hypertrophic genes, the level of oxidative stress, the expression of optic atrophy 1 (OPA1), dynamin related protein 1 (DRP1) and mitogen activated protein kinase (MAPK, including ERK, P38 and JNK) phosphorylation were measured. Results In WT mice, NaHS significantly reduced the cardiac index of ISO induced mice, decreased the cross sectional area of cardiomyocytes, inhibited the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA. The activity of total antioxidant capacity and superoxide dismutase (SOD) in the myocardium were increased but the level of malondialdehyde (MDA) was decreased. The fluorescence intensity of dihydroethidium staining for superoxide anion was attenuated. OPA1 expression were up regulated, but DRP1 expression and ERK phosphorylation were down regulated. However, all above protective effects on ISO induced cardiac hypertrophy were available in SIRT3 deficiency mice. Conclusions H2S inhibited ISO induced cardiac hypertrophy depending on SIRT3, and the possible mechanisms might be associated with antioxidant stress.
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