Dexmedetomidine Mitigates Myocardial Ischemia/Reperfusion-Induced Mitochondrial Apoptosis through Targeting lncRNA HCP5

Am J Chin Med. 2022;50(6):1529-1551. doi: 10.1142/S0192415X22500641. Epub 2022 Aug 4.

Abstract

Our study aimed to explore the function and mechanism of Dexmedetomidine (Dex) in regulating myocardial ischemia/reperfusion (I/R)-induced mitochondrial apoptosis through lncRNA HCP5. We demonstrated Dex suppressed I/R-induced myocardial infarction and mitochondrial apoptosis in vivo. Dex induced the expression of lncRNA HCP5 and MCL1, inhibited miR-29a expression and activated the JAK2/STAT3 signaling. Dex attenuated hypoxia/reoxygenation (H/R)-induced mitochondrial apoptosis by upregulating lncRNA HCP5 in cardiomyocytes. Overexpression of lncRNA HCP5 sponged miR-29a to suppress H/R-induced mitochondrial apoptosis. Knockdown of miR-29a also alleviated cardiomyocyte apoptosis by upregulating MCL1. Overexpression of lncRNA HCP5 activated the JAK2/STAT3 signaling through sponging miR-29a and enhancing MCL1 expression in cardiomyocytes. Dex mitigated myocardial I/R-induced mitochondrial apoptosis through the lncRNA HCP5/miR-29a/MCL1 axis and activation of the JAK2/STAT3 signaling.

Keywords: Dexmedetomidine; LncRNA HCP5; MCL1; MiR-29a; Mitochondrial Apoptosis; Myocardial Ischemia/Reperfusion Injury.

MeSH terms

  • Apoptosis
  • Dexmedetomidine* / pharmacology
  • Humans
  • MicroRNAs* / genetics
  • Mitochondria / drug effects
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Myocardial Ischemia* / genetics
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / genetics
  • Myocardial Reperfusion Injury* / metabolism
  • Myocytes, Cardiac / metabolism
  • RNA, Long Noncoding* / genetics

Substances

  • HCP5 long noncoding RNA, human
  • MCL1 protein, human
  • MIRN29a microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • RNA, Long Noncoding
  • Dexmedetomidine