Hydrogen sulfide attenuates cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation in rats.
ABSTRACT Hydrogen sulfide (H2S) has been recently found to be an endogenous signaling gasotransmitter. Cardiac hypertrophy often develops in the course of heart failure. It is unknown whether or not endogenous H2S protects cardiac hypertrophy. This study was conducted to examine the effects of H2S on cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation and to explore its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups: normal, sham, abdominal aortic coarctation (AAC), AAC treated with enalapril and AAC treated with H2S. One week after surgery, enalapril and sodium hydrosulfide (NaHS)-treated rats were fed for 28 consecutive days and sacrificed. After that, the left ventricle mass index (LVMI), cardiomyocyte size and areas, collagen volume fraction (CVF) of the rats were measured. In the AAC rats, the LVMI, the cardiomyocyte size and areas, and the CVF were all markedly increased while in the H2S groups they were significantly reduced. H2S decreased the levels of Ang-II in the heart, but not in plasma. In addition, H2S also improved the expression of connexin 43 (Cx43). Our results suggest that H2S can significantly suppress cardiac hypertrophy and fibrosis induced by overloaded pressure, possibly by inhibiting the activity of intracardiac Ang-II and by modifying expression of Cx43.
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ABSTRACT: Introduction: Hydrogen sulfide (H2S) has been reported to inhibit myocardial hypertrophy in a cell model of cardiomyocyte hypertrophy. Our previous study also shows an H2S-induced increase in glucose me-tabolism in insulin-targeting cells. The present study aims to examine the hypothesis that H2S attenuates myocardial hypertrophy by promoting glucose utilization in cardiomyocytes. Methods: The cell model of cardiomyocyte hypertrophy was induced by application of phenylephrine and cardiomyocyte hypertrophy was examined using leucine incorporation assay. Protein levels were mea-sured using Western blot analysis. The activity of related enzymes was measured with enzyme-linked immunosorbent assay (ELISA). Results: NaHS (an H2S donor) treatment increased the activity of cultured cardiomyocytes and reduced hypertrophy in cultured cardiomyocytes at concentrations ranging from 25 to 200 μmol/L. NaHS treat-ment increased glucose uptake and the efficiency of glycolysis and the citric acid cycle. The key enzymes in these reactions, including lactate dehydrogenase and pyruvate kinase and succinate dehydrogenase, were activated by NaHS treatment (100 μmol/L). Some intermediates of glycolysis and the citric acid cycle, including lactic acid, cyclohexylammonium, oxaloacetic acid, succinate, L-dimalate, sodium citrate, cis-aconitic acid, ketoglutarate and DL-isocitric acid trisodium also showed anti-hypertrophic effects in cardiomyocytes. Conclusions: H2S improves glucose utilization and inhibits cardiomyocyte hypertrophy.Nitric Oxide 12/2014; 46. DOI:10.1016/j.niox.2014.12.007 · 3.18 Impact Factor
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ABSTRACT: Hydrogen sulfide (H2S) is a well-known toxic gas with the characteristic smell of rotten eggs. It is synthesized endogenously in mammals from the sulfur-containing amino acid L-cysteine by the action of several distinct enzymes: cystathionine-γ-lyase (CSE), cystathionine-ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) along with cysteine aminotransferase (CAT). In particular, CSE is considered to be the major H2S-producing enzyme in the cardiovascular system. As the third gasotransmitter next to nitric oxide (NO) and carbon monoxide (CO), H2S plays an important role in the regulation of vasodilation, angiogenesis, inflammation, oxidative stress and apoptosis. Growing evidence has demonstrated that this gas exerts a significant protective effect against the progression of cardiovascular diseases by a number of mechanisms such as vasorelaxation, inhibition of cardiovascular remodeling and resistance to form foam cells. The aim of this review is to provide an overview of the physiological functions of H2S and its protection against several major cardiovascular diseases, and to explore its potential health and therapeutic benefits. A better understanding will help develop novel H2S-based therapeutic interventions for these diseases.Clinica Chimica Acta 07/2014; 437. DOI:10.1016/j.cca.2014.07.012 · 2.76 Impact Factor
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ABSTRACT: Cardiac fibroblasts are crucial in pathophysiology of the myocardium whereby their aberrant proliferation has significant impact on cardiac function. Hydrogen sulphide (H2 S) is a gaseous modulator of potassium channels on cardiomyocytes and has been reported to attenuate cardiac fibrosis. Yet, the mechanism of H2 S in modulating proliferation of cardiac fibroblasts remains poorly understood. We hypothesized that H2 S inhibits proliferative response of atrial fibroblasts through modulation of potassium channels. Biophysical property of potassium channels in human atrial fibroblasts was examined by whole-cell patch clamp technique and their cellular proliferation in response to H2 S was assessed by BrdU assay. Large conductance Ca(2+) -activated K(+) current (BKCa ), transient outward K(+) current (Ito ) and inwardly rectifying K(+) current (IKir ) were found in human atrial fibroblasts. Current density of BKCa (IC50 = 69.4 μM; n = 6), Ito (IC50 = 55.1 μM; n = 6) and IKir (IC50 = 78.9 μM; n = 6) was significantly decreased (P < 0.05) by acute exposure to NaHS (a H2 S donor) in atrial fibroblasts. Furthermore, NaHS (100-500 μM) inhibited fibroblast proliferation induced by transforming growth factor-β1 (TGF-β1; 1 ng/ml), Ang II (100 nM) or 20% FBS. Pre-conditioning of fibroblasts with NaHS decreased basal expression of Kv4.3 (encode Ito ), but not KCa1.1 (encode BKCa ) and Kir2.1 (encode IKir ). Furthermore, H2 S significantly attenuated TGF-β1-stimulated Kv4.3 and α-smooth muscle actin expression, which coincided with its inhibition of TGF-β-induced myofibroblast transformation. Our results show that H2 S attenuates atrial fibroblast proliferation via suppression of K(+) channel activity and moderates their differentiation towards myofibroblasts.Journal of Cellular and Molecular Medicine 08/2013; 17(10). DOI:10.1111/jcmm.12114 · 3.70 Impact Factor