Müge Akbulut, Arzu Keskin Aktan, Gizem Sonugür, Saadet Özen Akarca, Aslı Nur Bahar, Hatice Kavak, Gonca Akbulut
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引用次数: 0
Abstract
Background: A primary factor in the pathogenesis of aging is oxidative stress, with cardiac inflammation and fibrosis being contributed to by increased oxidative stress as organisms age. Oxidative stress enhances the cardiac fibrotic signaling pathway, with reactive oxygen species inducing cardiac fibrosis through increased expression of the profibrotic factor transforming growth factor-beta 1 (TGF-β1). Furthermore, Wnt/β-catenin signaling pathway is implicated in interstitial fibrosis, which is associated with TGF-β. Sirtuin 2 (SIRT2) is expressed in heart tissue, with protective effects in pathological cardiac hypertrophy. We aimed to investigate the mechanisms of cardiac fibrosis in D-Galactose (D-Gal)-induced accelerated aging, focusing on TGF-β1, β-catenin, and SIRT2.
Methods: A total of 30 young male Sprague-Dawley rats were randomly divided into 4 groups: control group, D-Gal group, D-Gal + 4% dimethyl sulfoxide (DMSO) group, and D-Gal + the SIRT2 inhibitor (AGK2) group. After 10 weeks, the rats were sacrificed, and their hearts were removed. SIRT2 expression levels were measured by western blot and gene expression levels of TGF-β1 and β-catenin by quantitative real-time polymerase chain reaction.
Results: Transforming growth factor-beta 1 (TGF-β1) mRNA expression in heart tissue was higher in the D-Gal group compared to all other groups. β-catenin mRNA expression was higher in the D-Gal group than in the D-Gal + AGK2 group. SIRT2 protein expression was higher in the D-Gal + DMSO group compared to the control group. Sirtuin 2 expression was lower in the D-Gal + AGK2 group compared to the D-Gal and D-Gal + DMSO groups.
Conclusion: Sirtuin 2 inhibition attenuates fibrosis, as evidenced by the downregulation of TGF-β1 and β-catenin. Thus, targeting SIRT2 may represent a potential therapeutic strategy for diseases characterized by cardiac fibrosis in the future.
期刊介绍：
The Anatolian Journal of Cardiology is an international monthly periodical on cardiology published on independent, unbiased, double-blinded and peer-review principles. The journal’s publication language is English.
The Anatolian Journal of Cardiology aims to publish qualified and original clinical, experimental and basic research on cardiology at the international level. The journal’s scope also covers editorial comments, reviews of innovations in medical education and practice, case reports, original images, scientific letters, educational articles, letters to the editor, articles on publication ethics, diagnostic puzzles, and issues in social cardiology.
The target readership includes academic members, specialists, residents, and general practitioners working in the fields of adult cardiology, pediatric cardiology, cardiovascular surgery and internal medicine.
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