Journal ArticleOpen Access
Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice
Authors
Fei Xue, Jing Cheng, Yan Liu, Cheng Cheng, …
Author Affiliations
Shandong University, Chinese Academy of Medical Sciences & Peking Union Medical College, Capital Medical University, Beijing Chao-Yang Hospital, Capital Medical University, ...
Published InSignal Transduction and Targeted Therapy
Year2022
Citations118
Abstract
Abstract Angiotensin-converting enzyme 2 (ACE2) has proven beneficial in attenuating diabetic cardiomyopathy (DCM) but has been found to be a substrate of a disintegrin and metalloprotease protein-17 (ADAM17). However, whether ADAM17 plays a role in the pathogenesis and intervention of DCM is obscure. In this study, we created cardiomyocyte-specific knockout of ADAM17 (A17 α-MHCKO ) mice, and left ventricular dimension, function, pathology and molecular biology were assessed in ADAM17 fl/fl control, A17 α-MHCKO control, ADAM17 fl/fl diabetic and A17 α-MHCKO diabetic mice. Both differentiated H9c2 cells and neonatal rat cardiomyocytes (NRCMs) were used to explore the molecular mechanisms underlying the effect of ADAM17 on DCM. The results showed that protein expression and activity of ADAM17 were upregulated whereas the protein…
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