Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic cardiomyopathy by downregulating autophagy
نویسندگان
چکیده
Myocardial fibrosis is one of the most important pathological features of alcoholic cardiomyopathy (ACM). Hydrogen sulfide (H2S) exerts protective effects in various types of cardiovascular disease, which has been demonstrated by many previous studies. However, there is a lack of adequate research on the effect of H2S on myocardial fibrosis in ACM. The present study aimed to investigate the etiopathogenic role of H2S in myocardial fibrosis induced by chronic alcohol intake. An ACM mouse model was induced by consumption of 4% ethanol solution in drinking water for 12 weeks. Sodium hydrosulfide (NaHS) was used as a donor to provide exogenous H2S. Twelve weeks later, mice were sacrificed to calculate the heart to body weight ratio. The degree of myocardial collagen deposition was evaluated by Masson's and Van Gieson's staining, the expression level of collagen Ⅰ was measured by immunohistochemistry and autophagosomes were observed by transmission electron microscopy. In addition, the expression levels of autophagy‑associated proteins and fibrosis-associated proteins were detected by western blotting, and the expression levels of miR-21 and miR-211 were detected by reverse transcription-quantitative polymerase chain reaction. The outcomes of the study revealed that chronic alcohol intake results in myocardial fibrosis, enhanced myocardial collagen deposition and increased expression levels of collagen I, autophagy, autophagy-associated proteins (Beclin 1, Atg3 and Atg7) and fibrosis-associated proteins (MMP8, MMP13, MMP14, MMP17 and TGF-β1), as well as miR-21 and miR-221. These results were markedly reversed following treatment with H2S. The present study confirmed that H2S relieves myocardial fibrosis in mice with ACM, and the underlying mechanism may involve the downregulation of autophagy and miR-21 and miR-211 expression levels.
منابع مشابه
Effects of hydrogen sulfide on myocardial fibrosis and PI3K/AKT1-regulated autophagy in diabetic rats.
Myocardial fibrosis is the predominant pathological characteristic of diabetic myocardial damage. Previous studies have indicated that hydrogen sulfide (H2S) has beneficial effects in the treatment of various cardiovascular diseases. However, there is little research investigating the effect of H2S on myocardial fibrosis in diabetes. The present study aimed to investigate the effects of H2S on ...
متن کاملMyocardial fibrosis delineation in late gadolinium enhancement images of Hypertrophic Cardiomyopathy patients using deep learning methods
Introduction: Accurate delineation of myocardial fibrosis in Late Gadolinium Enhancement on Cardiac Magnetic Resonance (LGE-CMR) has a crucial role in the assessment and risk stratification of HCM patients. As this is time-consuming and requires expertise, automation can be essential in accelerating this process. This study aims to use Unet-based deep learning methods to automate the mentioned ...
متن کاملToll-Like Receptor (TLR) 2 and TLR4 Differentially Regulate Doxorubicin Induced Cardiomyopathy in Mice
Recent evidence indicates that toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of dilated cardiomyopathy (DCM), but the exact mechanisms of their actions have not been elucidated. We explored the therapeutic potential of blocking TLRs in mice with established cardiomyopathy. Cardiomyopathy was generated by a single intraperitoneal injection of doxorubicin (10 mg/kg). Two weeks...
متن کاملHydrogen sulfide protects coriander seedlings against copper stress by regulating the ascorbate-glutathione cycle, in leaves
Heavy metals are the cause of major abiotic stresses in plants and a principal contributor to environmental pollution in recent decades. This study investigated the effects of exogenous hydrogen sulfide on the ascorbate-glutathione cycle in the leaves of coriander seedlings under copper stress. Results showed that copper stress not only reduced APX and GR activities but also decreas...
متن کاملAlcohol-induced myocardial fibrosis in metallothionein-null mice: prevention by zinc supplementation.
Alcohol-induced cardiomyopathy including fibrosis has been recognized clinically for a long time, but its pathogenesis is incompletely understood. Studies using experimental animals have not fully duplicated the pathological changes in humans, and animal models of alcoholic cardiac fibrosis are not available. In the present study, we have developed a mouse model in which cardiac hypertrophy and...
متن کامل