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Poster Abstract PresentationsSession Title: Poster Session 3

Abstract 342: Implication Of Mir-98 In The Cardiac Vulnerability Of Pregnancy To Ischemia Reperfusion Injury

Jingyuan Li, Zoltan Pierre Arany, Mansoureh Eghbali
Circulation Research. 2014;115:A342
Jingyuan Li
UCLA, Los Angeles, CA
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Zoltan Pierre Arany
Beth Israel Deaconess Med Ctr, Boston, CA
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Mansoureh Eghbali
UCLA, Los Angeles, CA
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Abstract

We have recently reported that the late-pregnant(LP) rodent is more prone to myocardial ischemia-reperfusion (I/R) injury compared to non-pregnant(NP). However, the underlying molecular mechanisms involved in the higher susceptibility of LP to IR injury are not quite clear. The objective of this study was to investigate the role of miRNA-98(miR-98) in higher cardiac vulnerability to I/R injury in late pregnancy. NP and LP(19 days of pregnancy Sprague-Dawley rats were subjected to 45 min myocardial ischemia followed by 3 hr reperfusion in vivo (I/R group). NP and LP rats which were not subjected to I/R injury served as controls. MicroRNA microarray expression were performed. In vitro, miR-98 was knocked down or overexpressed in neonatal rat ventricular myocytes(NRVMs). Forty eight hour post-transfection, the cells were subjected to 3 hr hypoxia followed by 12 hr reoxygenation. The apoptosis was detected by TUNEL staining, and the western blot was performed to validate the computational predicted targets genes, PGC-1α and STAT3. The miRNA expression profile showed that several miRNAs were differentially expressed in LP sham compared to NP sham, particularly, miR-98 which was significantly upregulated 1.7 fold in LP sham vs NP sham. Interestingly, miR-98 was upregulated even higher (2.3 folds) in LP rats when subjected to ischemia/reperfusion injury compared to NP I/R, suggesting that both ischemia reperfusion and late pregnancy regulate miR-98. Knock down of miRNA-98 in NRVMs significantly reduced apoptosis by ~50%, while over-expression of miR98 resulted in a two fold increase in apoptosis. In-vitro overexpression of miR98-KD in NRVMS resulted in the a significant upregulation of PGC-1α(normalized to scramble control, 1.34±0.04, P<0.05) and STAT3(normalized to scramble control, 1.28±0.05, P<0.05), whereas overexpression of miR-98 resulted in downregulation of both target genes(normalized to scramble control, 0.75±0.02 in PGC-1α; 0.5±0.03 in STAT3, both P<0.05). In conclusion, induction of miR-98 by pregnancy possibly through downregulating PGC-1α and STAT3 may at least in part underlie the greater cardiac vulnerability to I/R injury in late pregnancy.

  • Cardioprotection
  • Ischemia reperfusion
  • Apoptosis
  • Author Disclosures: J. Li: None Z. Arany: None M. Eghbali: None.

  • © 2014 by American Heart Association, Inc.
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Circulation Research
July 18, 2014, Volume 115, Issue Suppl 1
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    Abstract 342: Implication Of Mir-98 In The Cardiac Vulnerability Of Pregnancy To Ischemia Reperfusion Injury
    Jingyuan Li, Zoltan Pierre Arany and Mansoureh Eghbali
    Circulation Research. 2014;115:A342, originally published November 6, 2014

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    Abstract 342: Implication Of Mir-98 In The Cardiac Vulnerability Of Pregnancy To Ischemia Reperfusion Injury
    Jingyuan Li, Zoltan Pierre Arany and Mansoureh Eghbali
    Circulation Research. 2014;115:A342, originally published November 6, 2014
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