Hydrogen Sulfide as a Potential Alternative for the Treatment of Myocardial Fibrosis

Abstract

Harmful, stressful conditions or events in the cardiovascular system result in cellular damage, inflammation, and fibrosis. Currently, there is no targeted therapy for myocardial fibrosis, which is highly associated with a large number of cardiovascular diseases and can lead to fatal heart failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter similar to nitric oxide and carbon monoxide. H2S is involved in the suppression of oxidative stress, inflammation, and cellular death in the cardiovascular system. The level of H2S in the body can be boosted by stimulating its synthesis or supplying it exogenously with a simple H2S donor with a rapid- or slow-releasing mode, an organosulfur compound, or a hybrid with known drugs (e.g., aspirin). Hypertension, myocardial infarction, and inflammation are exaggerated when H2S is reduced. In addition, the exogenous delivery of H2S mitigates myocardial fibrosis caused by various pathological conditions, such as a myocardial infarct, hypertension, diabetes, or excessive β-adrenergic stimulation, via its involvement in a variety of signaling pathways. Numerous experimental findings suggest that H2S may work as a potential alternative for the management of myocardial fibrosis. In this review, the antifibrosis role of H2S is briefly addressed in order to gain insight into the development of novel strategies for the treatment of myocardial fibrosis.

Effects of Hydrogen Sulfide Donor NaHS on Porcine Vascular Wall-Mesenchymal Stem Cells

“…Recent interest has been addressed to the role of H 2 S in the field of mesenchymal stem cells (MSCs), so the use of H 2 S donors has been proposed to treat various pathological situations such as osteoporosis, immune disorders, inflammation and cardiovascular disease [17][18][19][20][21]. However, some H 2 S donors' adverse effects were evidenced in different cell types [10][11][12], therefore, for the safe therapeutic use of these molecules, it is necessary to consider first that very different effects could depend on the context.…”

“…In pathological models, the treatment with H₂S donors could increase the proliferation and survival of MSCs attenuating hypoxia-induced apoptosis by enhancing the antiapoptotic gene expression [ 18 , 19 ]. Moreover, it has also been reported that H₂S improved the survival of transplanted MSCs into infarcted myocardium in a rat model [ 20 ] and exerted an antifibrosis role in cardiovascular disease [ 21 ].…”

Cardiac Protection by Oral Sodium Thiosulfate in a Rat Model of L-NNA-Induced Heart Disease

“…H 2 S markedly prevented the development of cardiac fibrosis and decreased the collagen content in the cardiac tissue by inhibiting the activity of intracardiac angiotensin II (Huang et al, 2012). In addition, the suppression of inflammation, the reduction of cardiac apoptosis from oxidative stress and improving mitochondrial derangements are likely to have antifibrotic roles under hypertensive conditions (Wang et al, 2011;Kang et al, 2020). Antihypertensive effects of H 2 S, via modulation of channel activities and the cGMP/PKG pathways, may also contribute to the suppression of fibrosis caused by hypertension (Meng et al, 2015).…”

Triglyceride–Glucose Index and Extracellular Volume Fraction in Patients With Heart Failure

“…Cardiovascular magnetic resonance (CMR) imaging has emerged as a novel, non-invasive diagnostic tool to assess myocardial fibrosis (11), a key pathological process in HF (12). The importance of myocardial fibrosis to predict the prognosis in different cohorts of patients had been reported (13); however, there are limited clinical data on the interaction between insulin resistance and myocardial fibrosis in patients with HF.…”