Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Inhibition of Pathological Myofibroblast Differentiation of Valvular Interstitial Cell by Atorvastatin, Olmesartan, and Resveratrol in Experimental Heart Valve Model “Contemporary Model with Rabbit Valve”

Version 1 : Received: 30 August 2022 / Approved: 31 August 2022 / Online: 31 August 2022 (02:55:06 CEST)

How to cite: Suwanto, D.; Lefi, A.; Dharmadjati, B. B.; Oktaviono, Y. H.; Subagjo, A.; Sativa, O.; Rachmi, D. A.; Nugraha, R. A. Inhibition of Pathological Myofibroblast Differentiation of Valvular Interstitial Cell by Atorvastatin, Olmesartan, and Resveratrol in Experimental Heart Valve Model “Contemporary Model with Rabbit Valve”. Preprints 2022, 2022080529. https://doi.org/10.20944/preprints202208.0529.v1 Suwanto, D.; Lefi, A.; Dharmadjati, B. B.; Oktaviono, Y. H.; Subagjo, A.; Sativa, O.; Rachmi, D. A.; Nugraha, R. A. Inhibition of Pathological Myofibroblast Differentiation of Valvular Interstitial Cell by Atorvastatin, Olmesartan, and Resveratrol in Experimental Heart Valve Model “Contemporary Model with Rabbit Valve”. Preprints 2022, 2022080529. https://doi.org/10.20944/preprints202208.0529.v1

Abstract

Introduction. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p<0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

Keywords

Myofibroblast; Atorvastatin; Olmesartan; Resveratrol; Valvular Interstitial Cell

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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