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Zhan Gao,1,2 Yun Ti,1 Bin Lu,1 Fang-qiang Song,1,3 Lei Zhang,1 Bo-ang Hu,1 Jia-ying Xie,1 Wei Zhang,1 Lu Han,1,4 Ming Zhong1 1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Qilu College of Medicine, Shandong University, Jinan, Peopleâs Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Peopleâs Republic of China; 3Department of Critical Care Medicine, Tengzhou Central Peopleâs Hospital, Tengzhou, Peopleâs Republic of China; 4Department of General Practice, Qilu Hospital, Qilu College of Medicine, Shandong University, Jinan, Peopleâs Republic of ChinaCorrespondence: Lu Han; Ming Zhong, Email luhan_sdu@163.com; zhongming2sdu@163.comBackground: Previous studies have reported that six transmembrane protein of prostate 2 (STAMP2) attenuates metabolic inflammation and insulin resistance in diabetes mellitus. However, the role of STAMP2 in the diabetic heart is still unclear.Methods: A diabetic rat cardiomyopathy model was established via intraperitoneal STZ injection. STAMP2 was overexpressed in the treatment group using adeno-associated virus. Rat heart diastolic function was measured using echocardiography and a left ventricular catheter, and cardiac interstitial fibrosis was detected by immunohistochemistry and histological staining. Insulin sensitivity and NF-κB expression were shown by Western blotting. NMRAL1 distribution was illustrated by immunofluorescence.Results: STAMP2 expression in the diabetic rat heart was reduced, and exogenous overexpression of STAMP2 improved glucose tolerance and insulin sensitivity and alleviated diastolic dysfunction and myocardial fibrosis. Furthermore, we found that NF-κB signaling is activated in the diabetic heart and that exogenous overexpression of STAMP2 promotes NMRAL1 translocation from the cytoplasm to the nucleus and inhibits p65 phosphorylation.Conclusion: STAMP2 attenuates cardiac dysfunction and insulin resistance in diabetic cardiomyopathy, likely by promoting NMRAL1 retranslocation and NF-κB signaling inhibition.Keywords: STAMP2, diabetic cardiomyopathy, NADPH, NMRAL1, NF-κB |
