Retracted: AT1R knockdown confers cardioprotection against sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway in rats

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.

Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction

“…Secondly, by inhibiting the autophagy, TG 50 and TG 100 mg/kg protected the cardiac cell from the cardiac injury, which was induced by sepsis. Thirdly, TG 50 and TG 100 mg/kg dose suppressed the PTEN to inhibit the autophagy in cardiac cells by activating the AKT/mTOR signaling mechanism [8,9].…”

Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model

“…In addition, it has been established that silencing AT1R plays an inhibitory role in the SCM by blocking the MAPK signaling pathway (demonstrated as reduced extracellular signal-regulated kinase and cyclic adenosine 3′,5′-monophosphate response element binding protein expressions, and decreased concentrations of TnI, troponin T, and creatine kinase-MB) [ 40 ]. Therefore, DIZE may also mitigate SCM through diminished myocardial AT1R expression by mechanisms other than promoting the ACE2/Ang-(1–7)/MasR pathway.…”

Clinical value of microRNA-378a-3p in sepsis and its role in sepsis-induced inflammation and cardiac dysfunction

“…From this, we obtained that sepsis fundamentally affected the systolic and diastolic functions of the myocardium. cTnI and CK-MB are commonly used in clinical evaluation of myocardial status and are specific markers of myocardial injury [ 29 , 30 ]. We noticed that the levels of cTnI and CK-MB were increased in the serum of CLP group, suggesting the cardiac dysfunction of sepsis rat was accompanied by the occurrence of myocardial injury.…”