Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease

Authors

  • Mahdieh Khanahmadi Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • Babak Manafi Department of Surgery, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • Heidar Tayebinia Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • Jamshid Karimi Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • Iraj Khodadadi Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan-Iran. Tel: +9881 38380572; Fax: +9881 38380208. E-mail: khodadadi@umsha.ac.ir; ikhodadadi@yahoo.com

DOI:

https://doi.org/10.17179/excli2020-2423

Keywords:

apoptosis, atherosclerosis, coronary artery disease, epicardial adipose tissue, Sirt1, p53

Abstract

The higher expression level of p53 in epithelial adipose tissue (EAT) has previously been reported in atherosclerosis. Since we hypothesized that the expression of p53 is modulated by Sirt1, the aim of this study was to determine the expression levels of Sirt1 and p53 and to investigate their correlation to apoptosis in EAT of patients with coronary artery disease (CAD). Thirty-five patients with more than 50 % stenosis in at least one of the main coronary arteries were considered as CAD group while 29 patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as control group. EAT biopsy samples were collected from all participants during surgery. Sirt1, p53, Bax, and Bcl‑2 gene expression levels were determined in EAT by qRT-PCR and Western blotting was carried out to assess Sirt1 and p53 protein levels. Hematoxylin and eosin staining was used for histopathological analysis. mRNA and protein levels of Sirt1 in EAT were significantly lower in patients with CAD compared with control group, whereas CAD patients showed greater p53 gene and protein expressions. In addition, inverse correlations were observed between Sirt1 and p53 at both mRNA and protein levels. The Bax and ratio of Bax/Bcl-2 gene expressions were higher in CAD group, but no difference was observed in Bcl-2 expression. Histopathological analysis showed apoptotic bodies and infiltrated immune cells in EAT of CAD group. Our results suggest that the Sirt1-p53 axis may involve in atherosclerosis by promotion of apoptosis.

Downloads

Published

2020-10-02

How to Cite

Khanahmadi, M., Manafi, B., Tayebinia, H., Karimi, J., & Khodadadi, I. (2020). Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease. EXCLI Journal, 19, 1387–1398. https://doi.org/10.17179/excli2020-2423

Issue

Vol. 19 (2020)

Section

Original articles

License

Copyright (c) 2020 Mahdieh Khanahmadi, Babak Manafi, Heidar Tayebinia, Jamshid Karimi, Iraj Khodadadi

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish in this journal agree to the following terms:

  • The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
  • The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
  • Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
  • The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).