AEBP1 exacerbates myocardial ischemia-reperfusion injury via inhibition of IκBα
Abstract
Myocardial ischemia/reperfusion injury (MIRI) remains a main reason for death after cardiovascular diseases. Up-regulation of adipocyte enhancer binding protein 1 (AEBP1) has been found in ischemic cardiomyopathy patients. However, its influence and detailed mechanisms in MIRI are obscure. In this study, expression of target molecules was determined by RT-qPCR and Western blotting. Cell viability and apoptosis were evaluated by CCK-8 and TUNEL. Inflammatory cytokine levels were assessed by ELISA. Myocardial function and pathological changes were examined by echocardiography and HE staining. Cardiac infarct size was determined by TTC staining. Our data indicated that oxygen-glucose deprivation/reoxygenation (OGD/R) resulted in high expression of AEBP1, while low expression of IκBα in cardiomyocytes. In vitro data indicated that AEBP1 knockdown increased viability, inhibited apoptosis, and inflammation in H9c2 cells under OGD/R. AEBP1 interacted with IκBα to cause IκBα degradation, and facilitated the nuclear translocation of NF-κB. Moreover, IκBα silencing attenuated siAEBP1-medaited inhibition in inflammation and apoptosis of OGD/R-treated H9c2 cells, suggesting that IκBα was involved in the pro-inflammatory action of AEBP1. Finally, deficiency of AEBP1 mitigated MIRI in rats through IκBα/NF-κB pathway. Taken together, AEBP1 exacerbated MIRI through repressing IκBα expression to trigger NF-κB-mediated inflammation.
Keywords: myocardial ischemia-reperfusion injuryAEBP1IκBαNF-κBinflammationapoptosis
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