miRNA-30 Family Inhibition Protects Against Cardiac Ischemic Injury by Regulating Cystathionine-γ-Lyase Expression

Abstract

Aims: Myocardial infarction (MI) is a leading cause of death globally. MicroRNAs (miRNAs) have been identified as a novel class of MI injury regulators. Hydrogen sulfide (H 2 S) is a gaseous signaling molecule that regulates cardiovascular function. The purpose of this study was to explore the role of the miR-30 family in protecting against MI injury by regulating H 2 S production. Results: The expression of miR-30 family was upregulated in the murine MI model as well as in the primary cardiomyocyte hypoxic model. However, the cystathionine-c-lyase (CSE) expression was significantly decreased. The overexpression of miR-30 family decreased CSE expression, reduced H 2 S production, and then aggravated hypoxic cardiomyocyte injury. In contrast, silencing the whole miR-30 family can protect against hypoxic cell injury by elevating CSE and H 2 S level. Nonetheless, the protective effect was abolished by cotransfecting with CSE-siRNA. Systemic delivery of a locked nucleic acid (LNA)-miR-30 family inhibitor correspondingly increased CSE and H 2 S level, then reduced infarct size, decreased apoptotic cell number in the peri-infarct region, and improved cardiac function in response to MI. However, these cardioprotective effects were absent in CSE knockout mice. MiR-30b overexpression in vivo aggravated MI injury because of H 2 S reduction, and this could be rescued by Spropargyl-cysteine (SPRC), which is a novel modulator of CSE, or further exacerbated by propargylglycine (PAG), which is a selective inhibitor of CSE. Innovation and Conclusion: Our findings reveal a novel molecular mechanism for endogenous H 2 S production in the heart at the miRNA level and demonstrate the therapeutic potential of miR-30 family inhibition for ischemic heart diseases by increasing H 2 S production. Antioxid. Redox Signal. 22,[224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240]

Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

“…In the field of cardiac research, research on the miR-30 family is mainly focused on myocardial hypertrophy, myocardial infarction, heart failure and ischemia reperfusion injury [27-29]. The miR-30 family also plays an important role in the inhibition of cardiac ischemic injury [30]. The results of this study showed that mi-30e-3p expression is significantly decreased after CME, meanwhile, myocardial autophagy is dramatically inhibited.…”

Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation

“…As one of the endogenous H 2 S synthases, CSE is critical for H 2 S homeostasis. Previous research by our group and other groups demonstrated that plasma H 2 S levels in CSE -/ -mice decreased by *50% compared with those in wild-type (WT) mice (17,44). Thus, we compared the hepatic Hamp response between WT and CSE -/ -mice.…”

“…Quantification of H 2 S concentration H 2 S determination was performed using the methylene blue method as described previously (44).…”

Protective effect of microRNA-30b on hypoxia/reoxygenation-induced apoptosis in H9C2 cardiomyocytes

“…Other studies showed that miR-106b is an antiapoptosis regulator and inhibits p21 expression, while miR-15b controls anti-angiogenic activity, suggesting that these two miRs may be robust regulators of apoptosis or angiogenesis relevant in myocardial infarction (Liu et al, 2012). MiR-30b has been implicated in cardiovascular pathophysiology such as the angiotensin II-induced myocardial hypertrophy, myocardial matrix remodeling, sprouting angiogenesis, and Ang II-induced cardiomyocyte apoptosis (Shen et al, 2014). NFκB positively regulates the expression of miR-30b and Bcl-2 in Angiotensin II-induced cardiomyocytes apoptosis, therefore miR-30b is suspected to play a regulatory role in apoptotic pathways (Wei et al, 2014).…”