SIRT3-mediated mitochondrial autophagy in refeeding syndrome-related myocardial injury in sepsis rats

Abstract

Background: Myocardial injury induced by refeeding syndrome (RFS) is one of the important causes of deterioration in critically ill patients. Sirtuin-3 (SIRT3) has been shown to regulate mitochondrial autophagy in myocardial ischemia/reperfusion injury; however, the role of mitochondrial autophagy on RFS-related myocardial injury in patients in critical condition has not been reported on.Methods: Thirty Sprague-Dawley (SD) rats were divided into 3 groups (n=10 each group): the control group; the standard calorie refeeding (SCR) group; and the low calorie refeeding (LCR) group. The rats were weighed every third or four days from day 1 to day 14. On day 14, all rats were anesthetized and received an echocardiography test. Blood and bronchoalveolar lavage fluid (BALF) were collected and tested for arterial oxygen pressure (PaO 2 ), phosphorus (P), and calcium (Ca), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin 1 (cTnI), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6. The histopathological change of hearts and lungs were evaluated, and lung injury score was calculated. Mitochondrial autophagy related proteins (including Beclin1, LC3, mitofusin-2, Mfn2, PINK1, Parkin, and SIRT3) were analyzed using a Western blot. To evaluate the effect of SIRT3, 20 rats were divided into 2 groups (n=10 each group): The adeno-associated virus 9 (AAV9-Nc) group; and the AAV9-SIRT3 overexpression (AAV9-SIRT3) group. The protocols for rats were the same as the SCR group since day 22 after injection of AAV9. The protein expressions of PINK1, Parkin, and SIRT3 were compared between the AAV9-Nc group and AAV9-SIRT3 group.Results: SCR caused significant decline in cardiac contractility and increased inflammatory cell infiltration in myocardial tissue. Meanwhile, Beclin1, LC3, PINK1, Parkin, and SIRT3 levels decreased, while Mfn2 showed no significant change. Furthermore, significant positive correlations were also found between SIRT3 and P, PINK1, and Parkin, and significant negative correlations were found between SIRT3 and CK-MB, LDH, and cTnI. Overexpression of SIRT3 activated the PINK1/Parkin mediated mitochondrial autophagy.Conclusions: SIRT3 has an essential role in RFS-related myocardial injury during LPS induced chronic sepsis in rats, probably via regulating mitochondrial autophagy.

Early plasma proteomic biomarkers and prediction model of acute respiratory distress syndrome after cardiopulmonary bypass: a prospective nested cohort study

“…After reperfusion, left lung tissue and serum were obtained. The severity of lung injury was scored using a semiquantitative scoring system as described previously 27 , 28 . Please refer to Method A.6 (Supplemental Digital Content 1, http://links.lww.com/JS9/A835 ) for further details.…”

The Current State of Research on Sirtuin-Mediated Autophagy in Cardiovascular Diseases

“…For instance, remote ischemic preconditioning activates SIRT3/hypoxia-inducible factor 1-α and inhibits autophagy, thereby exerting cardioprotective effects [ 103 ]. SIRT3 plays an essential role in refeeding syndrome-related myocardial injury during lipopolysaccharide-induced chronic sepsis in rats, possibly via the regulation of PINK/Parkin-mediated mitochondrial autophagy [ 104 ]. Low levels of SIRT6 expression have been found to be associated with increased all-cause mortality and notable adverse cardiovascular events in patients with acute myocardial infarction, and the activation of SIRT6-mediated autophagy has been shown to protect endothelial cells from post-ischemic inflammation [ 86 ].…”