Eplerenone Reverses Age-Dependent Cardiac Fibrosis by Downregulating Osteopontin

Document Type : Original Article

Authors

1 Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

2 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

3 Faculty of Biology, Genetic group. North Tehran Branch, Islamic Azad University, Tehran, IR Iran.

Abstract

Purpose: The risk of cardiovascular disease increases dramatically with aging. It is now fully understood that fibrotic remodeling is the primary cause of cardiac structural and functional changes related to the normal aging process. However, the related signaling pathways and mechanisms are not completely understood. Therefore, finding new therapeutic approaches targeting cardiac fibrotic remodeling may be necessary to develop preventive care in the geriatric population against cardiovascular diseases. In this study, we evaluated the potential role of osteopontin (OPN) as a novel mediator of age-dependent fibrotic pathways in the heart, as well as the effect of eplerenone on cardiac fibrosis reversal.
 
Methods: Fischer-344 (F-344) rats were used in 3 groups: young rats (2–3 months old), aged rats (22-24 months old) without any treatment, and aged rats treated with eplerenone (100 mg/kg/day) for 2 weeks. The mRNA expression level of OPN was evaluated using real-time PCR, and histological assessments were done to assess cardiac tissue fibrosis.
 
Results: The expression level of OPN was significantly higher in aged rats than in young rats. Treatment with eplerenone significantly attenuated the level of OPN and cardiac fibrosis compared with untreated aged rats.
 
Conclusions: Targeting cardiac fibroblast function with eplerenone could decrease the expression of the OPN marker and reverse age-related cardiac fibrotic changes. (Iranian Heart Journal 2024; 25(2): 6-14)

Keywords

References

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Iranian Heart Journal
Volume 25, Issue 2
March 2024
Pages 6-14

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