Dexamethasone and olmesartan as potential antiremodelling agents of valvular interstitial cell into myofibroblast

Ardianto Nandiwardhana; Denny Suwanto; Eka Prasetya Budi Mulia; David Nugraha; Achmad Lefi; Mohammad Budiarto; Johanes Nugroho

doi:10.53730/ijhs.v6nS9.12283

Authors

Ardianto Nandiwardhana
wardhanaaddo@gmail.com
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia
Denny Suwanto Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia
Eka Prasetya Budi Mulia Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia
David Nugraha Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia
Achmad Lefi Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia
Mohammad Budiarto Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia
Johanes Nugroho Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Surabaya, Indonesia

Keywords:

Valvular interstitial cell, myofibroblast, α-Smooth muscle actin, dexamethasone, Olmesartan

Abstract

Rheumatic heart disease is a late complication of valvular inflammation caused by rheumatic fever. Studies have shown that the differentiation of valvular interstitial cells (VIC) into fibroblasts plays an important role in valvular remodeling and fibrosis. Various strategies to minimize valvular fibrosis has increased recently. This study aims to analyze the effect of dexamethasone, olmesartan, and its combination in inhibiting TGF-β1-induced VIC differentiation into myofibroblast. In vitro laboratory experimental-posttest only control group design was conducted. Isolated VIC of Oryctolagus cuniculus was pretreated using 2,5 ng/mL of TGF-β1 and divided into groups of dexamethasone (0.1 uM/L), olmesartan (100 nmol/L), and its combination. Inhibition of myofibroblast differentiation was quantified by the expression of α-SMA levels detected by immunoﬂuorescence. Dexamethasone, olmesartan, and its combination administration were significantly reduced TGF-β1-induced VIC differentiation into myofibroblast expressed by α-SMA levels (dexamethasone 6823 ± 1735.3, olmesartan 6683.7 ± 2795.05). Combination of dexamethasone and olmesartan exhibit the most potent inhibition compared to control (5051.87 ± 1612.210 vs 22286.73 ± 2780.2; p < 0.000). In conclusion, dexamethasone, olmesartan, and the combination can significantly reduce the differentiation of VIC into myofibroblasts. The greatest potential is the combined effect of dexamethasone and olmesartan, while dexamethasone and olmesartan have the same potential.

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