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Myocardial ischaemia/reperfusion injury (MIRI) remains a major cause of death after cardiovascular diseases. Up-regulation of adipocyte enhancer binding protein 1 (AEBP1) has been found in ischaemic 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 indicate that oxygen-glucose deprivation/ reoxygenation (OGD/R) resulted in high expression of AEBP1 but low expression of IκBα in cardiomyocytes. In vitro data indicate that AEBP1 knockdown increased viability, and 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.

Citation

Wei-Na Xue. Adipocyte enhancer binding protein 1 exacerbates myocardial ischaemia-reperfusion injury via inhibition of IκBα. Folia morphologica. 2024;83(3):656-666

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PMID: 37957937

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