Therapeutic effects of KANK2 in myocardial infarction rats might be associated with the NF-κB p65 inhibition.

Lin Li, Zai-Bo Li, Min Jia, Hong-Tao Chu

International immunopharmacology 2020 Sep

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KN motif and ankyrin repeat domains 2 (KANK2) may inhibit the activation of (NF-kappaB) p65, which plays a role in myocardial injury. Thus, our study aims to discover the effect of KANK2 on myocardial infarction (MI) induced by ligating the left anterior descending coronary artery (LAD) through regulating NF-κB p65 in vivo. MI rats underwent LAD ligation were administered with intramyocardial injections of KANK2/Control activation plasmids. Six weeks after MI, pressure-volume (P/V) loops was used to investigate the cardiac function of rats, then the following detections were performed, including TTC staining, HE staining, immunofluorescence, Masson' s trichrome staining, ELISA assay, TUNEL staining, immunohistochemistry, qRT-PCR and Western blotting. MI rats decreased in maximum pressure (pmax), ejection fraction (EF%), peak rate of pressure rise (dpdtmax) and decline (-dpdtmax) with increased end diastolic pressure (EDP), which was partially reversed by KANK2 overexpression. Besides, KANK2 CRISPR activation plasmids reduced infarct size with less collagen fiber proliferation and neutrophil infiltration in infarct tissues, as well as suppressed pro-inflammatory factors expressions in MI rats. Moreover, injection of KANK2 activation plasmid decreased collagen deposition, aggravated cardiomyocyte apoptosis, enhanced the capillary density, and increased the expressions of VEGF and bFGF in the infarct and peri-infarct regions of MI rats. KANK2 lowered myocardial NF-κB p65 expression in MI rats. KANK2 may play its therapeutic role in MI through improving cardiac function, decreasing myocardial collagen deposition, reducing cardiomyocyte apoptosis, and increasing angiogenesis, which might be associated with the reduction of NF-κB p65 expression. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Lin Li, Zai-Bo Li, Min Jia, Hong-Tao Chu. Therapeutic effects of KANK2 in myocardial infarction rats might be associated with the NF-κB p65 inhibition. International immunopharmacology. 2020 Sep;86:106687