Annexin-A1 short peptide alleviates septic myocardial injury by upregulating SIRT3 and inhibiting myocardial cell apoptosis
Song Qin1, Yingcong Ren1, Banghai Feng2, Xiaoqin Wang3, Junya Liu1, Jie Zheng4, Kang Li1, Hong Mei1, Qiuyu Dai4, Hong Yu1 and Xiaoyun Fu1
1Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, 2Department of Critical Care Medicine, Zunyi Hospital of Traditional Chinese Medicine, 3Department of Pediatric, The Second Affiliated Hospital of Zunyi Medical University and 4Zunyi Medical University, Zunyi, Guizhou, PR China
Corresponding Author: Xiaoyun Fu, Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, PR China. e-mail: xiaoyunfu666@163.com
Summary. Septic myocardial injury is a common complication of severe sepsis, which occurs in about 50% of cases. Patients with this disease may experience varying degrees of myocardial damage. Annexin-A1 short peptide (ANXA1sp), with a molecular structure of Ac-Gln-Ala-Tyr, has been reported to exert an organ protective effect in the perioperative period by modulating sirtuin-3 (SIRT3). Whether it possesses protective activity against sepsis-induced cardiomyopathy is worthy of study. This study aimed to investigate whether ANXA1sp exerts its anti-apoptotic effect in septic myocardial injury in vitro and in vivo via regulating SIRT3. In this study, we established in vivo and in vivo models of septic myocardial injury based on C57BL/6 mice and primary cardiomyocytes by lipopolysaccharide (LPS) induction. Results showed that ANXA1sp pretreatment enhanced the seven-day survival rate, improved left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and cardiac output (CO), and reduced the levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Western blotting results revealed that ANXA1sp significantly increased the expression of SIRT3, Bcl-2, and downregulated Bax expression. TUNEL staining and flow cytometry results showed that ANXA1sp could attenuate the apoptosis rate of cardiomyocytes, whereas this anti-apoptotic effect was significantly attenuated after SIRT3 knockout. To sum up, ANXA1sp can alleviate LPS-induced myocardial injury by reducing myocardial apoptosis via SIRT3 upregulation. Histol Histopathol
Key words: Septic myocardial injury, Sirtuin-3, Annexin-A1 short peptide, Apoptosis
DOI: 10.14670/HH-18-691
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©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
