It is noteworthy that prolonged cardiac structural changes and excessive fibrosis caused by myocardial infarction (MI) seriously interfere with the treatment of heart failure in clinical practice. Currently, there are no effective and practical means of either prevention or treatment. Thus, novel therapeutic approaches are critical for the long‐term quality of life of individuals with myocardial ischaemia. Herein, we aimed to explore the protective effect of H2, a novel gas signal molecule with anti‐oxidative stress and anti‐inflammatory effects, on cardiac remodelling and fibrosis in MI rats, and to explore its possible mechanism. First, we successfully established MI model rats, which were then exposed to H2 inhalation with 2% concentration for 28 days (3 hours/day). The results showed that hydrogen gas can significantly improve cardiac function and reduce the area of cardiac fibrosis. In vitro experiments further proved that H2 can reduce the hypoxia‐induced damage to cardiomyocytes and alleviate angiotensin II‐induced migration and activation of cardiac fibroblasts. In conclusion, herein, we illustrated for the first time that inhalation of H2 ameliorates myocardial infarction‐induced cardiac remodelling and fibrosis in MI rats and exert its protective effect mainly through inhibiting NLRP3‐mediated pyroptosis.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a critical process in various cardiovascular diseases such as coronary artery disease (CAD), atherosclerosis, stroke, and hypertension. MicroRNAs (miRNAs) are small, short, and noncoding RNAs that inhibit gene expression through binding to the 3'-UTR (3' untranslated regions) of target gene mRNAs. We showed that the expression of miR-448 was upregulated in VSMCs from coronary atherosclerotic plaques compared with normal coronary artery tissues. We also found that PDGF-bb promoted VSMCs proliferation and could induce miR-448 expression. Ectopic miR-448 expression induced VSMCs proliferation. Overexpression of miR-448 induced ki-67 mRNA and protein expression. Moreover, we identified MEF2C was a direct target of miR-448 in VSMCs. Overexpression of miR-448 promoted VSMCs migration. Furthermore, overexpression of MEF2C decreased miR-448-induced VSMCs proliferation and migration. These evidences suggested that miR-448 played an important role in the proliferation and migration of VSMCs.

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Background: Continuous damage from oxidative stress and apoptosis are the important mechanisms that facilitate chronic heart failure (CHF). Molecular hydrogen (H2) has potentiality in the aspects of anti-oxidation. The objectives of this study were to investigate the possible mechanism of H2 inhalation in delaying the progress of CHF.Methods and Results: A total of 60 Sprague-Dawley (SD) rats were randomly divided into four groups: Sham, Sham treated with H2, CHF and CHF treated with H2. Rats from CHF and CHF treated with H2 groups were injected isoprenaline subcutaneously to establish the rat CHF model. One month later, the rat with CHF was identified by the echocardiography. After inhalation of H2, cardiac function was improved vs. CHF (p < 0.05), whereas oxidative stress damage and apoptosis were significantly attenuated (p < 0.05). In this study, the mild oxidative stress was induced in primary cardiomyocytes of rats, and H2 treatments significantly reduced oxidative stress damage and apoptosis in cardiomyocytes (p < 0.05 or p < 0.01). Finally, as a pivotal transcription factor in reactive oxygen species (ROS)-apoptosis signaling pathway, the expression and phosphorylation of p53 were significantly reduced by H2 treatment in this rat model and H9c2 cells (p < 0.05 or p < 0.01).Conclusion: As a safe antioxidant, molecular hydrogen mitigates the progression of CHF via inhibiting apoptosis modulated by p53. Therefore, from the translational point of view and speculation, H2 is equipped with potential therapeutic application as a novel antioxidant in protecting CHF in the future.

microRNAs (miRNAs or miRs) play important roles in modulating the occurrence and progression of atherosclerosis and acute coronary syndrome (ACS). Herein, this study aimed to investigate the possible role of miR-9 in the development of atherosclerosis. Initially, the differentially expressed genes associated with ACS were screened and miRNAs that regulate syndecan-2 (SDC2) were predicted using microarray analysis. Furthermore, the biological functions of miR-9 and SDC2 on aortic plaque area, proliferation of collagen fibers, Mac-3-labeled macrophages, inflammatory response, and levels of the focal adhesion kinase/extracellular signal-regulated kinase (FAK/ERK) signaling pathway-related proteins in atherosclerosis were evaluated after ectopic miR-9 expression or SDC2 depletion in ACS mice using oil red O staining, Masson’s trichrome staining, immunohistochemistry, and Western blot analysis, respectively. SDC2 was highly-expressed, while miR-9 was poorly-expressed in atherosclerosis. Additionally, miR-9 targeted SDC2 and negatively-regulated its expression. Up-regulation of miR-9 reduced aortic plaque area, the proliferation of collagen fibers, Mac-3-labeled macrophages and levels of IL-6, IL-1β, and TNF-α by suppressing SDC2 and the FAK/ERK signaling pathway, thereby ameliorating atherosclerosis in ACS mice. In conclusion, the current study provides evidence that miR-9 retards atherosclerosis by repressing SDC2 and the FAK/ERK signaling pathway, highlighting a new theoretical basis for the treatment of atherosclerosis.