miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-γ-lyase expression.

Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 100888899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7716 (Electronic) Linking ISSN: 15230864 NLM ISO Abbreviation: Antioxid Redox Signal Subsets: MEDLINE

Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., 1999-

Cystathionine gamma-Lyase/*metabolism ; MicroRNAs/*genetics ; Myocardial Ischemia/*enzymology; Animals ; Base Sequence ; Binding Sites ; Cystathionine gamma-Lyase/genetics ; Enzyme Repression ; HEK293 Cells ; Humans ; Hydrogen Sulfide/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Myocytes, Cardiac/metabolism ; RNA Interference ; Rats, Sprague-Dawley

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.

PLoS One. 2013;8(1):e53950. (PMID: 23326547)
Antioxid Redox Signal. 2010 May 15;12(10):1203-17. (PMID: 19769484)
Antioxid Redox Signal. 2010 May 15;12(10):1155-65. (PMID: 19842912)
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15560-5. (PMID: 17878306)
Essays Biochem. 2013;54:29-38. (PMID: 23829525)
Antioxid Redox Signal. 2012 Jul 1;17(1):141-85. (PMID: 22304473)
J Biol Chem. 2009 Oct 23;284(43):29514-25. (PMID: 19706597)
Circ Res. 2009 Jan 30;104(2):170-8, 6p following 178. (PMID: 19096030)
PLoS One. 2013 Oct 23;8(10):e77047. (PMID: 24194857)
Circ Res. 2012 Jan 6;110(1):71-81. (PMID: 22052914)
J Cardiovasc Pharmacol. 2009 Aug;54(2):139-46. (PMID: 19546814)
Herz. 2014 Mar;39(2):194-200. (PMID: 24573748)
J Appl Physiol (1985). 2007 Jan;102(1):261-8. (PMID: 17038495)
Circ Cardiovasc Genet. 2014 Jun;7(3):311-20. (PMID: 24825878)
Antioxid Redox Signal. 2012 Jul 1;17(1):106-18. (PMID: 22017202)
Cell Death Dis. 2013 Oct 10;4:e845. (PMID: 24113179)
Breast Cancer Res Treat. 2012 Aug;134(3):1081-93. (PMID: 22476851)
J Mol Cell Cardiol. 2012 Jan;52(1):13-20. (PMID: 21801730)
Nat Genet. 2011 Mar 20;43(4):371-8. (PMID: 21423181)
Nat Med. 2007 Apr;13(4):486-91. (PMID: 17401374)
Physiol Genomics. 2007 Nov 14;31(3):367-73. (PMID: 17712037)
Circulation. 2011 Aug 9;124(6):720-30. (PMID: 21788589)
Biomed Pharmacother. 2006 Nov;60(9):607-20. (PMID: 16952435)
Biochem Biophys Res Commun. 2004 Jun 4;318(3):756-63. (PMID: 15144903)
Genes Dev. 2004 Mar 1;18(5):504-11. (PMID: 15014042)
Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1211-7. (PMID: 10749716)
Acta Physiol Hung. 2011 Dec;98(4):369-81. (PMID: 22173019)
Circulation. 2010 Jul 6;122(1):11-9. (PMID: 20566952)
Biochem Biophys Res Commun. 2011 Sep 23;413(2):342-7. (PMID: 21893044)
Circulation. 2007 Jul 17;116(3):258-67. (PMID: 17606841)
Circ Res. 2007 Feb 16;100(3):416-24. (PMID: 17234972)
Mol Cell Biochem. 2014 Feb;387(1-2):135-41. (PMID: 24178239)
PLoS One. 2012;7(12):e50926. (PMID: 23236408)
Circ J. 2009 Jul;73(7):1171-7. (PMID: 19506318)
Blood. 2012 Dec 13;120(25):5063-72. (PMID: 23086751)
PLoS Biol. 2005 Mar;3(3):e85. (PMID: 15723116)
Biosci Rep. 2011 Apr;31(2):87-98. (PMID: 20450490)
Am J Pathol. 2013 Apr;182(4):1448-58. (PMID: 23410520)
J Cell Physiol. 2012 Sep;227(9):3192-200. (PMID: 22034194)
Antioxid Redox Signal. 2009 Apr;11(4):703-14. (PMID: 18855522)
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13027-32. (PMID: 18723672)
Circulation. 2012 Aug 14;126(7):840-50. (PMID: 22811578)
N Engl J Med. 2007 Sep 13;357(11):1121-35. (PMID: 17855673)
FASEB J. 2002 Nov;16(13):1792-8. (PMID: 12409322)
Cell. 2004 Jan 23;116(2):281-97. (PMID: 14744438)
Int J Biol Sci. 2012;8(4):430-41. (PMID: 22419888)

0 (MIRN30b microRNA, human)
0 (MicroRNAs)
EC 4.4.1.1 (Cystathionine gamma-Lyase)
YY9FVM7NSN (Hydrogen Sulfide)

Date Created: 20140910 Date Completed: 20150910 Latest Revision: 20220317

20240104

PMC4283074

10.1089/ars.2014.5909

25203395