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 (H2S) 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 H2S 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-γ-lyase (CSE) expression was significantly decreased. The overexpression of miR-30 family decreased CSE expression, reduced H2S 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 H2S 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 H2S 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 H2S reduction, and this could be rescued by S-propargyl-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 H2S production in the heart at the miRNA level and demonstrate the therapeutic potential of miR-30 family inhibition for ischemic heart diseases by increasing H2S production.
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 (H2S) 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 H2S 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-γ-lyase (CSE) expression was significantly decreased. The overexpression of miR-30 family decreased CSE expression, reduced H2S 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 H2S 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 H2S 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 H2S reduction, and this could be rescued by S-propargyl-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 H2S production in the heart at the miRNA level and demonstrate the therapeutic potential of miR-30 family inhibition for ischemic heart diseases by increasing H2S production.
Authors: R D Rakhit; R J Edwards; J W Mockridge; A R Baydoun; A W Wyatt; G E Mann; M S Marber Journal: Am J Physiol Heart Circ Physiol Date: 2000-04 Impact factor: 4.733
Authors: Yi Zhun Zhu; Zhong Jing Wang; Peiying Ho; Yoke Yun Loke; Yi Chun Zhu; Shan Hong Huang; Chee Sin Tan; Matt Whiteman; Jia Lu; Philip K Moore Journal: J Appl Physiol (1985) Date: 2006-10-12
Authors: Stefano Toldo; Anindita Das; Eleonora Mezzaroma; Vinh Q Chau; Carlo Marchetti; David Durrant; Arun Samidurai; Benjamin W Van Tassell; Chang Yin; Ramzi A Ockaili; Navin Vigneshwar; Nitai D Mukhopadhyay; Rakesh C Kukreja; Antonio Abbate; Fadi N Salloum Journal: Circ Cardiovasc Genet Date: 2014-05-13
Authors: Daniel J Sassoon; Adam G Goodwill; Jillian N Noblet; Abass M Conteh; B Paul Herring; Jeanette N McClintick; Johnathan D Tune; Kieren J Mather Journal: Basic Res Cardiol Date: 2016-05-27 Impact factor: 17.165