MicroRNA-503 Exacerbates Myocardial Ischemia/Reperfusion Injury via Inhibiting PI3K/Akt-and STAT3-Dependent Prosurvival Signaling Pathways

Yanjing He, Yin Cai, Tianhao Sun, Liangqing Zhang, Michael G. Irwin, Aimin Xu, Zhengyuan Xia

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

Acute myocardial infarction is a leading cause of death worldwide, while restoration of blood flow to previously ischemic myocardium may lead to ischemia/reperfusion (I/R) injury. Accumulated evidence shows that microRNAs play important roles in cardiovascular diseases. However, the potential role of microRNA-503 (miR-503) in myocardial I/R injury is little known. Thus, this study is aimed at determining whether and how miR-503 affects myocardial I/R injury in vivo and in vitro. A mouse model of myocardial I/R injury and H9c2 cell model of hypoxia/reoxygenation (H/R) injury were established. The postischemic cardiac miR-503 was downregulated in vivo and in vitro. Mechanistically, PI3K p85 and Bcl-2 are miR-503 targets. The post-ischemic cardiac PI3K p85 protein level was decreased in vivo. Agomir-503 treatment exacerbated H/R-induced injuries manifested as decreased cell viability, increased lactate dehydrogenase activity, and cell apoptosis. Agomir-503 treatment reduced cell viability under normoxia as well and reduced both PI3K p85 and Bcl-2 protein levels under either normoxia or H/R condition. It reduced phosphorylation of Stat3 (p-Stat3-Y705) and Akt (T450) in cells subjected to H/R. In contrast, Antagomir-503 treatment attenuated H/R injury and increased p-Stat3 (Y705) under normoxia and increased p-Akt (T450) under either normoxia or H/R condition. It is concluded that miR-503 exacerbated I/R injury via inactivation of PI3K/Akt and STAT3 pathways and may become a therapeutic target in preventing myocardial I/R injury.

Original languageEnglish
Article number3449739
JournalOxidative Medicine and Cellular Longevity
Volume2022
DOIs
Publication statusPublished - 2022

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

Fingerprint

Dive into the research topics of 'MicroRNA-503 Exacerbates Myocardial Ischemia/Reperfusion Injury via Inhibiting PI3K/Akt-and STAT3-Dependent Prosurvival Signaling Pathways'. Together they form a unique fingerprint.

Cite this