Hsp22 ameliorates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidative stress, and apoptosis

Abstract

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.

Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

“…Experiments were carried out in this study to determine if the exogenous Ang-(1–7) pretreatment could regulate RAAS, and the outcome of these experiments showed that Ang-(1–7) effectively inhibits the biological function of Ang II, thereby alleviating SIC. Excessive inflammatory responses and oxidative stress can aggravate cardiomyocyte apoptosis and promote the occurrence and development of SIC [ 61 , 62 ]. We observed that the LPS stimulation resulted in an excessive inflammatory response, elevated ROS production, and increased cardiomyocyte apoptosis in the in vivo and in vitro SIC models.…”

Zataria multiflora and its constituent, carvacrol, counteract sepsis‐induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress

“…ROS promote the release of pro‐inflammatory mediators. The process in turn produces more ROS 5,6,9 . The vicious cycle has a detrimental effect on tissues by mediating mitochondrial disturbance, aggravating cellular damage and eventually leading to chronic diseases 5,9 …”

Hsp22 pretreatment protects against LPS-induced hippocampal injury by alleviating neuroinflammation and apoptosis by regulating the NLRP3/Caspase1/IL-1β signaling pathway in mice

“…Under stress conditions, this pathway mediates mitochondrial homeostasis, oxidative stress and apoptosis, and has cytoprotective activity, thereby accelerating the recovery of nerve function [ 61 ]. In addition, other studies have reported that Hsp22 inhibits oxidative stress-induced hippocampal neuronal cell death by regulating mitochondrial pathway and that Hsp22 improves lipopolysaccharide induced myocardial injury [ 62 , 63 ]. In contrast to existing studies, our study is the first to shows that Hsp22 targets the NLRP3/caspase-1/IL-1β pathway to improve LPS-induced cognitive impairment, that Hsp22 preconditioning reduces the LPS-induced inflammatory response and cell apoptosis and improves learning and memory impairment in mice.…”