Eplerenone Reverses Age-Dependent Cardiac Fibrosis Through Downregulating Osteopontin

Abstract Background: The risk of cardiovascular disease dramatically increases with Ageing. Nowadays it is fully revealed that the fibrotic remodelling is the main cause of cardiac structural and functional changes related to the normal aging process, but the related signaling pathways and mechanisms are incompletely understood. Thus finding the new therapeutic approaches targeting cardiac fibrotic remodelling, may be necessary to develop preventive care in geriatric population against cardiovascular diseases. In this study, we evaluated the potential role of osteopontin (OPN) as novel mediators of age-dependent fibrotic pathways in heart as well as the effect of eplerenone on cardiac fibrosis reversal. Methods: Fischer-344 (F-344) rats has been used as three groups: young rats (2–3months old), aged rats (22-24 months old) without any treatment and aged rats treated with eplerenone (100 mg/kg/day) for 2 weeks. The expression level of OPN has been evaluated using real-time PCR and histological assessments were done to assess cardiac tissue fibrosis.Results: The expression level of OPN in aged rats was significantly higher than young rats and treatment with eplerenone significantly attenuated the level of OPN as well as cardiac fibrosis compare to untreated aged rats. Conclusion: Targeting cardiac fibroblast function with eplerenone could decrease expression of OPN marker and cause to reversal age-related cardiac fibrotic changes.