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Adv Pharm Bull. 2023;13(1): 202-209.
doi: 10.34172/apb.2023.039
PMID: 36721814
PMCID: PMC9871268
  Abstract View: 698
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Research Article

Decreased Cardiac NOX4 and SIRT-1 Protein Levels Contribute to Decreased Angiogenesis in the Heart of Diabetic Rats: Rescue Effects of IGF-1 and Exercise

Shiva Roshan Milani 1,2 ORCID logo, Bagher Pourheydar 3,2, Saman Daneshfar 4, Leila Chodari 1,2* ORCID logo

1 Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
2 Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
3 Department of Anatomical Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
4 Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
*Corresponding Author: *Corresponding Author: Leila Chodari, Email: , Email: chodari.l@umsu.ac.ir

Abstract

Purpose: Reduced angiogenesis in the heart tissue is a primary risk factor for heart disease in the diabetes condition. This study was aimed to evaluate the changes of two main angiogenesis mediators, NADPH oxidase 4 (NOX4) and sirtuin 1 (SIRT-1) protein levels in the heart of diabetic rats and the impact of Insulin-like growth factor 1 (IGF-1) and exercise on these proteins.

Methods: Injection of 60 mg/kg of streptozotocin in 40 male Wistar rats led to the induction of type 1 diabetes. Angiogenesis was detected in the hearts by immunostaining for PECAM-1/ CD31 after 30 days of treatment with IGF-1 (2 mg/kg/day) and exercise. ELISA technique was utilized to establish the expression levels of NOX4 and SIRT-1 within the heart.

Results: The results revealed a significant increase in HbA1c and a significant decrease in SIRT1, NOX4 levels and angiogenesis grade in the heart of diabetes group compared to control group. Meanwhile, IGF-1 and exercise alone or in combination completely masked these effects. Additionally, synergistic effect on SIRT-1, HbA1c levels and angiogenesis grade is evident when IGF-1 and exercise are applied simultaneously.

Conclusion: Our findings suggest that reduction in angiogenesis in the heart of diabetic rats may be mediated by down expression of NOX4 and SIRT-1 protein levels. It was also displayed that IGF-1 and exercise as novel therapies increase NOX4 and SIRT-1 protein levels within the hearts of diabetic rats.

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Submitted: 16 Jun 2021
Revision: 22 Nov 2021
Accepted: 31 Dec 2021
ePublished: 03 Jan 2022
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