ABSTRACT
C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.
Subject(s)
Adipokines/genetics , Cell Hypoxia , Myocytes, Cardiac/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Oxygen/administration & dosage , Animals , Animals, Newborn , Apoptosis , Cell Survival , Cytokines/metabolism , Inflammation/metabolism , Mice , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , Reactive Oxygen Species/metabolism , Signal Transduction , Up-RegulationABSTRACT
OBJECTIVES: Percutaneous coronary interventions (PCIs) save countless acute myocardial infarction (AMI) patients. However, endothelial injury is still an inevitable complication. Circulating microparticles (MPs) play important roles in vascular dysfunction. Whether PCI affects function of MPs remains unclear. METHODS: MPs were obtained from AMI patients (nâ=â38) both preoperatively and 24âh after PCI, and healthy subjects (nâ=â20). MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs to determine the effects of MPs on phosphorylation of endothelial nitric oxide synthase (eNOS), caveolin-1 expression, eNOS association with heat shock protein 90 (Hsp90), generation of nitric oxide (NO) and superoxide anion (O2), and endothelial-dependent vasodilatation. RESULTS: Compared with healthy subjects, MP concentrations increased in AMI patients. Undergoing PCI had no further effect on MPs concentration, but it results in increased endothelial-derived MPs proportion and decreased platelet-derived MP ratio. MPs from AMI patients decreased eNOS phosphorylation at Ser1177, increased eNOS phosphorylation at T495 and caveolin-1 expression, decreased eNOS association with Hsp90, decreased NO production but increased (O2) generation, damaged endothelial-dependent vasodilatation. All of these effects of MPs were strengthened by PCI. CONCLUSIONS: PCI further enhances the vascular injury effect of MPs. Circulating MPs may be a potential therapeutic target for patients undergoing PCI.
