microRNA-181c-5p stimulates the development of coronary artery disease by targeting SIRT1
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese(2023)
摘要
Objective: MicroRNA (miR) therapeutics is a promising approach to manage coronary artery disease (CAD). Herein, this research was aimed to explore miR-181c-5p-related mechanisms in CAD through regulating SIRT1.Methods: A CAD mouse model was established by feeding a high-fat diet in 8-week-old ApoE-/- mice. miR-181c-5p, SIRT1, and acetylated p65 levels in mouse myocardial tissues were evaluated by RT-qPCR and Western blot. Hemodynamic parameters included the maximum rising rate of the left ventricular pressure (lv + dp/dtmax) and the time values from the onset of contraction to dp/dtmax (t-dp/dtmax), while hemorheological indices included whole blood viscosity (low shear, middle shear, or high shear), plasma viscosity, hematocrit, and platelet adhesion were measured. Tumor necrosis factor -a (TNF-a), interleukin-1b (IL-1b), and IL-6 were detected. Mouse pathological changes, degree of fibrosis, and cardiomyocyte apoptosis in myocardial tissues were assessed by HE, Masson, and TUNEL staining, respectively. The targeting relationship between miR-181c-5p and SIRT1 was verified by bioinformatics tools, dual luciferase reporter gene assay, and RNA pull-down assays.Results: In myocardial tissue of CAD mice, miR-181c-5p and acetylated p65 were upregulated while SIRT1 was downregulated. Downregulating miR-181c-5p or upregulating SIRT1 effectively ameliorated CAD by improving hemodynamics and hemorheology and reducing inflammation, pathological changes, degree of fibrosis, and cardiomyocyte apoptosis in myocardial tissues of mice. miR-181c-5p targeted SIRT1, and overexpression of SIRT1 relieved upregulated miR-181c-5p-induced injuries in CAD mice. Regulating miR-181c-5p and SIRT1 affected the acetylation of p65.Conclusion: Downregulation of miR-181c-5p may ameliorate myocardial pathological changes and car-diomyocyte apoptosis in CAD by upregulating SIRT1 expression and decreasing acetylated p65 levels.(c) 2022 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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关键词
Coronary artery disease,microRNA-181c-5p,Sirtuin 1,p65,Acetylation
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