SIRT3 attenuates coronary atherosclerosis in diabetic patients by regulating endothelial cell function |
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Authors: | Huiping Gong Jing Liu Zhiwei Xue Wenwen Wang Cuicui Li Fanfan Xu Yimeng Du Xiaona Lyu |
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Affiliation: | 1. Department of Emergency, The Second Hospital of Shandong University, Jinan China ; 2. Department of Cardiology, The Second Hospital of Shandong University, Jinan China ; 3. Cheeloo College of Medicine, Shandong University, Jinan China ; 4. Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan China |
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Abstract: | BackgroundThis study aimed to explore the relationship between the Sirtuin 3 (SIRT3) gene and endothelial cell dysfunction, contributing to the progression of coronary atherosclerosis driven by hyperglycemia.MethodsWe measured serum SIRT3 levels using enzyme‐linked immunosorbent assay in 95 patients with type 2 diabetes mellitus (T2DM) who underwent diagnostic coronary angiography. The patients were divided into two groups according to the presence (n = 45) or absence (n = 50) of coronary artery disease (CAD). Human aortic endothelial cells (HAECs) grown in vitro in a medium with various concentrations of glucose (5.5, 11, 16.5, 22, 27.5, 33, and 38.5 mM) for 24 h were assessed for protein expression of SIRT3, peroxisome proliferator‐activated receptor alpha (PPAR‐α), endothelial nitric oxide (NO) synthase (eNOS), and inducible NO synthase (iNOS) using Western blot analysis. HAECs were subjected to SIRT3 overexpression or inhibition through SIRT3 adenovirus and siRNA transfection.ResultsSerum SIRT3 levels were significantly lower in T2DM patients with CAD than in those without CAD (p = 0.048). The in vitro results showed that HG significantly increased SIRT3, PPAR‐α, and eNOS protein expression in a concentration‐dependent manner. Moreover, iNOS expression was decreased in HAECs in response to HG. Reduced PPAR‐α and eNOS levels and increased iNOS levels were observed in SIRT3 silenced HAECs cells. In contrast, SIRT3 overexpression significantly improved PPAR‐α and eNOS expression and suppressed iNOS expression.ConclusionSIRT3 was associated with the progression of atherosclerosis in T2DM patients through upregulation of PPAR‐α and eNOS and downregulation of iNOS, which are involved in endothelial dysfunction under hyperglycemic conditions. |
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Keywords: | atherosclerosis coronary artery disease diabetes endothelial dysfunction Sirtuin 3 |
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