Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

Despite an obnoxious smell and toxicity at a high dose, hydrogen sulfide (H₂S) is emerging as a cardioprotective gasotransmitter. H₂S mitigates pathological cardiac remodeling by regulating several cellular processes including fibrosis, hypertrophy, apoptosis, and inflammation. These encouraging findings in rodents led to initiation of a clinical trial using a H₂S donor in heart failure patients. However, the underlying molecular mechanisms by which H₂S mitigates cardiac remodeling are not completely understood. Empirical evidence suggest that H₂S may regulate signaling pathways either by directly influencing a gene in the cascade or interacting with nitric oxide (another cardioprotective gasotransmitter) or both. Recent studies revealed that H₂S may ameliorate cardiac dysfunction by upor downregulating specific microRNAs. MicroRNAs are noncoding, conserved, regulatory RNAs that modulate gene expression mostly by translational inhibition and are emerging as a therapeutic target for cardiovascular disease (CVD). Few microRNAs also regulate H₂S biosynthesis. The inter-regulation of microRNAs and H₂S opens a new avenue for exploring the H₂S-microRNA crosstalk in CVD. This review embodies regulatory mechanisms that maintain the physiological level of H₂S, exogenous H₂S donors used for increasing the tissue levels of H₂S, H₂S-mediated regulation of CVD, H₂S-microRNAs crosstalk in relation to the pathophysiology of heart disease, clinical trials on H₂S, and future perspectives for H₂S as a therapeutic agent for heart failure.