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Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway

  • Authors:
    • Min Zong
    • Hua Zhao
    • Qiang Li
    • Yanbing Li
    • Jianjun Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, P.R. China
    Copyright: © Zong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 117
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    Published online on: September 18, 2020
       https://doi.org/10.3892/etm.2020.9245
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Abstract

Myocardial fibrosis (MF) is an important pathological change in diabetic cardiomyopathy. The aim of the present study was to investigate whether irbesartan serves a role in improving MF in a diabetic rat model. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high‑density lipoprotein cholesterol (HDL‑C) and low‑density lipoprotein cholesterol (LDL‑C) levels were measured in rats using biochemical methods. Heart weight index (HWI), left ventricular weight index (LVWI), left ventricular systolic pressure (LVSP) and left ventricular end‑diastolic pressure (LVEDP) were also measured, whilst type I collagen and hydroxyproline content in myocardial tissue was quantified. Western blotting was used to measure the expression of transforming growth factor β1 (TGFβ1), phosphorylated (p)‑Smad2/3 and collagen type I α 1 chain (COL1A1) inmyocardial tissues or rat cardiac fibroblast (RCF) cells. Cell proliferation was measured using EdU staining. Procollagen type III N‑terminal peptide (PIIINP) content, FBG, TC, TG and LDL‑C levels were found to be significantly higher, whilst HDL‑C levels were found to be significantly lower in rats in the diabetic group. Those in the diabetic group also exhibited significantly elevated HWI, LVWI, LVEDP, myocardial tissue type I collagen content and hydroxyproline content values, but significantly reduced LVSP. Changes in the aforementioned indicators were reversed after treatment with irbesartan, where the protein expression levels of TGFβ1 and p‑Smad2/3 in myocardial tissue were also significantly reduced. In RCF cells, irbesartan significantly reversed high glucose‑induced upregulation of TGFβ1 expression, Smad2/3 phosphorylation and COL1A1 expression, as well as reducing cell proliferation and rat type I PICP and PIIINP levels. Application of pirfenidone produced additive effects on reducing the expression levels of the proteins aforementioned when combined with irbesartan. Therefore, the present results demonstrated that irbesartan reduced the activity of the TGFβ1/Smad2/3 pathway and ameliorated diabetic MF by downregulating the expression of TGFβ1.
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Copy and paste a formatted citation
Spandidos Publications style
Zong M, Zhao H, Li Q, Li Y and Zhang J: Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway. Exp Ther Med 20: 117, 2020.
APA
Zong, M., Zhao, H., Li, Q., Li, Y., & Zhang, J. (2020). Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway. Experimental and Therapeutic Medicine, 20, 117. https://doi.org/10.3892/etm.2020.9245
MLA
Zong, M., Zhao, H., Li, Q., Li, Y., Zhang, J."Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway". Experimental and Therapeutic Medicine 20.5 (2020): 117.
Chicago
Zong, M., Zhao, H., Li, Q., Li, Y., Zhang, J."Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway". Experimental and Therapeutic Medicine 20, no. 5 (2020): 117. https://doi.org/10.3892/etm.2020.9245
Copy and paste a formatted citation
x
Spandidos Publications style
Zong M, Zhao H, Li Q, Li Y and Zhang J: Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway. Exp Ther Med 20: 117, 2020.
APA
Zong, M., Zhao, H., Li, Q., Li, Y., & Zhang, J. (2020). Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway. Experimental and Therapeutic Medicine, 20, 117. https://doi.org/10.3892/etm.2020.9245
MLA
Zong, M., Zhao, H., Li, Q., Li, Y., Zhang, J."Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway". Experimental and Therapeutic Medicine 20.5 (2020): 117.
Chicago
Zong, M., Zhao, H., Li, Q., Li, Y., Zhang, J."Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway". Experimental and Therapeutic Medicine 20, no. 5 (2020): 117. https://doi.org/10.3892/etm.2020.9245
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