DOI: 10.1161/circ.148.suppl_1.18622 ISSN: 0009-7322

Abstract 18622: The Role of MicroRNA-98 in the Context of Myocardial Ischemia-Reperfusion Injury During Late Pregnancy

Laila Aryan, Lejla Medzikovic, Min Li, Gregoire Ruffenach, Shadie Rahman, Leana Esdin, Ehsan Bastanhagh, Wasila Sun, Yalda A Afshar, Mansoureh Eghbali
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

BACKGROUND: We have shown that the late-pregnant (LP) rodent exhibits a higher susceptibility to myocardial ischemia-reperfusion injury (IRI) compared to non-pregnant (NP). The molecular mechanisms remain unclear. The dysregulation of multiple microRNAs (miRs) in IRI suggests their potential as promising targets for therapeutic interventions.

Methods: Female Sprague-Dawley rats in both NP and LP states underwent occlusion of the left anterior descending coronary artery (LAD) for a duration of 45 minutes, followed by reperfusion for 3 hours or 24 hours. Expression of miR was assessed via fluorescent in situ hybridization. MicroRNA-microarray profiling was conducted on hearts of NP and LP rats subjected to IRI. Female H9c2 rat cardiomyoblast cells were transfected with miR mimics and inhibitors, and subjected to hypoxia/reoxygenation. Blood samples were obtained from NP, LP, and ischemic heart disease (IHD) patients. MiR98 inhibitor was administered at the initiation of reperfusion.

Results: MicroRNA-microarray analysis revealed upregulation of microRNA-98-5p (miR-98) in LV of LP at baseline, and a further upregulation after IRI. The expression of Stat3 and Pgc-1α were decreased in LV of LP rats compared to NP rats upon IRI. Fluorescent in situ hybridization revealed expression of miR-98 in cardiomyocytes in NP rats, which was increased in LP rats. Overexpression of miR-98 in vitro in female H9c2 cells decreased Stat3 and Pgc-1α levels, and promoted apoptosis, oxidative stress, and inflammatory markers. MiR-98 inhibitor in LP rats at the onset of reperfusion reduced infarct size, apoptosis, oxidative stress, and inflammatory markers and was associated with upregulation of Stat3 and Pgc-1α. In humans, plasma miR-98 levels were significantly higher in healthy LP compared to healthy NP individuals and even higher in LP patients with IHD patients.

CONCLUSIONS: We show the detrimental effects of miR-98 by promoting cardiomyocyte oxidative stress, inflammation, and apoptosis via its targets Stat3 and Pgc-1α in the context of late pregnancy. MiR-98 could be a novel cardio-protective strategy or biomarker in late pregnancy.

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