Abstract 72: Hydrogen Sulfide Prevents Myocardial Hypertrophy in a Klf5-dependent Manner
Rationale: H2S is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel-like transcription factor (KLF) exerts diverse functions in the cardiovascular system.
Objectives: The aim of present study was to investigate the effect of hydrogen sulfide (H2S) on myocardial hypertrophy.
Methods and results: Myocardial samples of 22 patients with left ventricle hypertrophy were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats (SHR) and neonatal rat cardiomyocytes were studied for functional and signaling response to GYY4137, a H2S-releasing compound. Expression of cystathionine -lyase (CSE), a main enzyme for H2S generation in human heart, decreased in human hypertrophic myocardium, while KLF5 expression increased. In SHR treated with GYY4137 for 4 weeks, myocardial hypertrophy was inhibited as evidenced by improvement in cardiac structural parameters, heart mass index, size of cardiac myocytes and expression of atrial natriuretic peptide (ANP). Levels of oxidative stress and phosphorylation of mitogen-activated protein kinases were also decreased after H2S treatment. H2S diminished expression of the KLF5 in myocardium of SHR and in neonatal rat cardiomyocytes rendered hypertrophy by angiotensin II (Ang II). H2S also inhibited ANP promoter activity and ANP expression in Ang II-induced neonatal rat cardiomyocyte hypertrophy, and these effects were suppressed by KLF5 knockdown. KLF5 promoter activity was increased by Ang II stimulation, and this was reversed by H2S. H2S also decreased activity of specificity protein-1 (SP-1) binding to the KLF5 promoter and attenuated KLF5 nuclear translocation by Ang II stimulation.
Conclusion: H2S attenuated myocardial hypertrophy, which might be related to inhibiting oxidative stress and decreasing ANP transcription activity in a KLF5-dependent manner.
Author Disclosures: G. Meng: None. L. Xie: None. Y. Ji: None.
- © 2015 by American Heart Association, Inc.