AT1R knockdown confers cardioprotection against sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway in rats
Authors: Ya-Ling Ma
Xiao-Zhe Wu
Bo Zhang
Hai-Tao Li
Tao Zhang
Xiang Ji
Yu Wang
Sheng Wu
Ya-Dan Li
Bin Zhang
Di Wu
Hong Li
Yu-Chao Yin
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: angiotensin II type 1 receptor; gene silencing; mitogen-activated protein kinase signaling pathway; myocardial injury; sepsis.
Affiliations: Intensive Care Unit Tianjin Huanhu Hospital Tianjin China, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases Tianjin China, Department of Neurosurgery Tianjin Huanhu Hospital Tianjin China, Department of Orthopedic Tianjin Medical University General Hospital Tianjin China

Abstract:  Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen-activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme-linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK-MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis-related proteins (Fas ligand [Fasl], B-cell CLL/lymphoma [Bcl-2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK-MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal-regulated kinase and cyclic adenosine 3',5'-monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK-MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl-2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway. 

Retracted: Yes

PubPeer comments:
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 21 August 2019 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. ------------------------------------------------------ The paper displays Western Blots of a stylised  string-of-sausages appearance. It was listed in [a spreadsheet dedicated to products of the Contractor papermill ] , but had not been flagged on Pubpeer. ![file] ,