Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice

• DOI: 10.1038/s41392-022-01054-3
• Publication Date: 2022-08-01T01:02:59Z
• Authors: Fei Xue; Jing Cheng; Yanping Liu; Cheng Cheng; Meng Zhang; Wenhai Sui; Wenqiang Chen; Panpan Hao; Yun Zhang; Cheng Zhang
• Keywords: Diabetic Cardiomyopathy; Knockout mouse

Abstract Angiotensin-converting enzyme 2 (ACE2) has proven beneficial in attenuating diabetic cardiomyopathy (DCM) but been found to be a substrate of disintegrin and metalloprotease protein-17 (ADAM17). However, whether ADAM17 plays role the pathogenesis intervention DCM is obscure. In this study, we created cardiomyocyte-specific knockout (A17 α-MHCKO ) mice, left ventricular dimension, function, pathology molecular biology were assessed fl/fl control, A17 mice. Both differentiated H9c2 cells neonatal rat cardiomyocytes (NRCMs) used explore mechanisms underlying effect on DCM. The results showed that protein expression activity upregulated whereas ACE2 was downregulated myocardium Cardiomyocyte-specific mitigated cardiac fibrosis cardiomyocyte apoptosis ameliorated dysfunction mice with Bioinformatic analyses detected number genes enriched metabolic pathways, particular AMPK signaling pathway, expressed differentially between hearts mechanism may involve activated increased autophagosome formation improved autophagic flux, which reduced apoptotic response cardiomyocytes. addition, hypoxia-inducible factor-1α (HIF-1α) might act as an upstream mediator affect via α1 A-adrenergic receptor (ADRA1A). These indicated shedding enhanced DCM, reversed by knockout. Thus, inhibition provide promising approach treatment