Adenosine Attenuates LPS-Induced Cardiac Dysfunction by Inhibition of Mitochondrial Function via the ER Pathway

Abstract

Sepsis is a life-threatening organ dysfunction syndrome with a high rate of mortality. It is caused by an abnormal immune response to infection, and the occurrence of sepsis-induced cardiomyopathy is the primary cause of death. The present study was designed to examine the effects of adenosine on lipopolysaccharide- (LPS-) induced cardiac anomalies and the underlying mechanisms involved. Adenosine (25, 50, and 100 mg/kg, i.g., 2 times/day) was administered for three days, followed by the induction of sepsis by intraperitoneal injection of LPS (10 mg/kg/2h). The effects of adenosine on inflammatory factors, LVEF, LVFS, and MAPK in septic rats (half male and half female) were observed. Subsequently, the effect of adenosine (10 μM) on the mitochondrial function of H9c2 cells stimulated with LPS (20 μg/mL, 24 h) was observed in the presence and absence of the estrogen receptor-specific antagonist ICI182,780. The results show that medium to high doses of adenosine can significantly promote cardiac function (LVEF and LVFS) and reduce the levels of inflammatory factors (TNF-α, IL-6, PCT, and cTnI) and p-JNK in septic rats, with a significant difference seen between male and female rats. The results of flow cytometry show that adenosine significantly inhibited increases in ROS levels, mitochondrial membrane potential, and the swelling degree of mitochondria in H9c2 cells stimulated with LPS, but this effect could be blocked by ICI182,780, indicating that adenosine attenuated LPS-induced cardiac dysfunction by inhibiting mitochondrial function via the ER pathway.

Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1

“…MAPK-p38 and NF-κB are important signaling pathways associated with myocardial cell injury ( 6 ). In the present study, to further verify the function of DUSP1, a cell model using H9C2 cells in which DUSP1 was downregulated was constructed ( Fig.…”

“…The pathological manifestations of sepsis-induced cardiomyopathy (SIc) are as follows: Spot hemorrhage on the myocardial surface, extensive myocardial hemorrhage, inflammatory cell infiltration, interstitial edema and degeneration and necrosis of some myocardial cells (2)(3)(4). during the process of sepsis, bacterial infection activates Toll-like receptor (TLR) via pathogen-related molecular patterns, such as lipopolysaccharide (LPS), thereby inducing MAPK and NF-κB pathway activation, which promotes the infiltration of inflammatory cells into myocardial tissue and triggers myocardial inhibition (5)(6)(7)(8)(9). Therefore, it is currently hypothesized that the inhibition of the NF-κB and MAPK pathways can effectively reduce the inflammatory response of the septic myocardium and is one of the strategies used to improve SIc.…”

Fangchinoline attenuates cardiac dysfunction in rats with endotoxemia via the inhibition of ERK1/2 and NF-κB p65 phosphorylation

“…Myocardial dysfunction in sepsis has multiple complex manifestations, including Original Article decreased ejection fraction and myocardial contractility. Additionally, previous studies have shown that the presence of acute cardiac dysfunction in sepsis is an indicator of poor prognosis (6,7).…”

“…In echocardiography, EF and FS are widely used as alternative markers of cardiac contractility and cardiac function. Zeng et al reported that high doses of adenosine could significantly improve LVEF and LVFS in LPSinduced septic rats(6). In this study, we first assessed the index effect of LVEF and LVFS in LPS-induced rats by echocardiography.…”

Paeoniflorin improves myocardial injury via p38 MAPK/NF-KB p65 inhibition in lipopolysaccharide-induced mouse

“…Septic myocardial dysfunction has complex manifestations, including reduced ejection fraction and myocardial contractility (5). Additionally, acute cardiac insufficiency is an indicator of poor prognosis in patients with sepsis (6,7).…”