Protective effect of Apelin/APJ system on lipopolysaccharide-related cardiac dysfunction

Abstract

At present, the pathogenesis of sepsis-induced myocardial dysfunction (SIMD) is not completely clear and effective treatment measures are lacking. Apelin is an endogenous ligand of the angiotensin like G protein coupled receptor APJ and a cardiovascular peptide with multiple functions. Our aim is to analyze the protective effect and mechanism of Apelin/APJ system on lipopolysaccharide (LPS)-induced myocardial dysfunction. One hour before LPS treatment, apelin-13 or an APJ antagonist [Ala]-apelin-13 (F13A) was given for pre-intervention to observe the effect of apelin-13 on cardiac ultrasound, pathological changes and inflammatory factors in LPS-treated mice. Another part of the mice was treated with apelin-13 or apelin-13 combined with F13A one hour after LPS treatment. The results showed that apelin-13 injection significantly reversed the decrease of ejection fraction and the increase of inflammatory factors induced by LPS in mice. Endogenous apelin may have protective effect on SIMD induced by LPS. Exogenous administration of apelin may inhibit LPS-induced inflammation, apoptosis and increase autophagy through TLR4/ERK1/2/NF-κB pathway.

Diagnostic and prognostic significance of apelin-13, APJ for sepsis in the emergency department: A prospective study

“…In this context, infusion of apelin-13 offers unique and optimized hemodynamic support, alongside cardioprotective effects and the modulation of circulatory inflammation, ultimately extending survival [ 34 ]. Apelin primarily exerts its effects on the cardiovascular system, particularly when myocardial injury occurs, by promoting apelin secretion to inhibit cardiac cell apoptosis, enhance myocardial contraction, and reduce myocardial injury [ 12 ]. Previous study has shown that the exogenous administration of apelin elicits positive inotropic effects in both healthy myocardium and in hearts affected by heart failure [ 29 ].…”

“…Several clinical investigations have substantiated that serum apelin-13 levels are elevated in septic patients, signifying its diagnostic value in the context of sepsis [ 11 ]. Furthermore, as sepsis frequently coincides with cardiomyocyte injury, animal studies have indicated that exogenous administration of apelin may mitigate inflammation, apoptosis, and augment autophagy in lipopolysaccharide-induced cardiac dysfunction [ 12 , 13 ]. Moreover, apelin-13 demonstrates the capacity to alleviate inflammatory responses induced by lipopolysaccharide and attenuate acute lung injury [ 14 , 15 ].…”

Apelin-13 Alleviates Hexavalent Chromium-Induced Myocardial Injury by Inhibiting ROS-mediated Oxidative Damage and Regulating Multiple Signals

“…K 2 Cr 2 O 7 -induced toxicity in H9c2 cells is a common cell model of Cr (VI) exposure to evaluate the cardioprotective pro les of bioactive reagents [6]. Apelin-13 can regulate the cardiovascular system [7]. Hence, the potential of apelin-13 was tested for its myocardiaprotective effect against toxicity induced by the toxins K 2 Cr 2 O 7 in H9c2 cells.…”

Inappropriate Activation of TLR4/NF-κB is a Cause of Heart Failure

“…A relationship exists between TLR4/NF-κB and autophagy. In myocardial injury caused by sepsis, TLR4/NF-κB increases the autophagy in myocardial cells, thereby damaging them [72]. When a specific inhibitor is used to inhibit TLR4 and NF-κB activity, myocardial injury markers, such as creatine kinase and lactate dehydrogenase, decline, and inflammatory cytokines, such as IL-6 and TNFα, are downregulated.…”