title: miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-γ-lyase expression.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: 1 Department of Pharmacology, School of Pharmacy, Fudan University , Shanghai, People's Republic of China .
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Shen
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Miao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xin
authors.forename: Shizhou
authors.initials: S
authors.lastname: Lin
authors.forename: Yichun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism*; D004794:Enzyme Repression; D057809:HEK293 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D017202:Myocardial Ischemia / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide