Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy

• Published in: Human & experimental toxicology 2021-05, Vol.40 (5), p.735-741
• Main Authors: Wang, Xiaofeng, Zhu, Yan, Zhou, Qiuxiang, Yan, Yueyue, Qu, Jinlong, Ye, Hongwei
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - metabolism; Animals; Apoptosis; Autophagy; Autophagy - drug effects; Cardiomyopathies - drug therapy; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathy; Cecum; Heat shock proteins; HSP70 Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - therapeutic use; Hsp70 protein; Humans; Inhibitors; Lipopolysaccharides; Male; Models, Animal; Phagocytosis; Quercetin; Quercetin - metabolism; Rats; Rats, Sprague-Dawley; Sepsis; Sepsis - complications; Sepsis - metabolism
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327120965758

Increasing evidence suggests that heat shock protein 70 (Hsp70) has a protective effect in sepsis-induced cardiomyopathy; however, the protective mechanism remains unclear. Previous studies have also implicated autophagy in sepsis-induced cardiomyopathy. The aim of the current study was to reveal the protective mechanisms of Hsp70 in sepsis-induced cardiomyopathy using a cecal ligation and puncture (CLP) rat sepsis model. The roles of Hsp70 and autophagy in sepsis-induced cardiomyopathy were investigated by pretreating rats with the Hsp70 inhibitor quercetin or the autophagy inhibitor 3-methyladenine (3-Ma) before CLP. We also investigated the protective mechanisms of Hsp70 and the relationship between Hsp70 and autophagy by stimulating H9c2 cells with lipopolysaccharide (LPS) to simulate sepsis. The result show that inhibition of Hsp70 promoted sepsis-induced death in rats, while inhibition of autophagy inhibited sepsis-induced death. These results suggested that both Hsp70 and autophagy were involved in sepsis-induced cardiomyopathy. Overexpression of Hsp70 in H9c2 myocardial cells suppressed LPS-induced apoptosis, while inhibition of autophagy with 3-Ma also decreased LPS-induced H9c2 cell apoptosis, suggesting that the protective effect of Hsp70 in sepsis-induced cardiomyopathy was related to autophagy regulation. Overall, these results suggested that Hsp70 protected against sepsis-induced cardiac impairment by attenuating sepsis-induced autophagy.