Drugs in the PipelineVaspin Prevents Tumor Necrosis Factor-α–Induced Apoptosis in Cardiomyocytes by Promoting AutophagyKe, Xuan MD; Hao, Yanqin MD; Li, Bingong PhD; Zou, Jin MD; Li, Xuelian MD; Wei, Chunying MD; Liu, Fuyou MD; Zhang, Zhiyong MDAuthor Information Department of Cardiology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China. Reprints: Bingong Li, PhD, Department of Cardiology, First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi, China (e-mail: [email protected]). Supported by the Science and Technology Program of Jiangxi Educational Committee (GJJ160022) and the National Natural Science Foundation of China (81460046). The authors report no conflicts of interest. X. Ke and Y. Hao contributed equally to this work. Journal of Cardiovascular Pharmacology: May 2018 - Volume 71 - Issue 5 - p 257-267 doi: 10.1097/FJC.0000000000000562 Buy Metrics Abstract Visceral adipose tissue–derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions. This study was designed to investigate the impact of vaspin on autophagy in tumor necrosis factor (TNF)-α–induced injury in cardiomyocytes and its cardioprotective effects in the pathogenesis of diabetic cardiomyopathy (DCM). H9C2 cells were treated with TNF-α with or without vaspin in vitro. Tumor necrosis factor-α treatment inhibited autophagy and promoted apoptosis in H9C2 cells after stimulating for 24 hours. Pretreatment with vaspin significantly mitigated apoptosis induced by TNF-α partly because of augment effects of vaspin on autophagy as demonstrated by a higher ratio of LC3-II/LC3-I, higher expression of Beclin-1, and increased autophagosomes formation. Furthermore, the AKT agonist IGF-1 significantly reversed the effect of vaspin on autophagy. In vivo DCM model was also developed by treating rats with streptozotocin followed by intraperitoneal injection with vaspin. In DCM rats, upregulation of vaspin reversed cardiac dysfunction, as identified by increased left ventricular ejection fractions and fractional shortening levels, a higher Em/Am ratio, and lower levels of TNF-α, lactate dehydrogenase, creatine kinase, and creatine kinase-myocardial isoenzyme. In conclusion, vaspin attenuated the TNF-α–induced apoptosis by promoting autophagy probably through inhibiting the PI3K/AKT/mTOR pathway and further ameliorated the cardiac dysfunction in DCM rats. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.