In Vitro Model of Valvular Fibrosis: Valve Interstitial Cells of Oryctolagus cuniculus Induced by Interleukin-۱β, Interleukin-۶, Transforming Growth Factor-β۱, and Tumor Necrosis Factor-α

Fibrosis of the heart valves is a progressive pathological process in rheumatic heart disease (RHD) that can cause permanent disability, characterized by valve interstitial cells (VICs) differentiation into myofibroblast. In rheumatic heart disease patients (RHD), heart valve cells contain substantially increased levels of high-sensitivity C-reactive protein (CRP), TGF-β۱, IL-۶, TNF-α, and IL-۱β, compared to those in healthy individuals. A variety of studies have illustrated TGF-β۱'s involvement in differentiating myofibroblasts from VICs, yet research on the influence of other cytokines in the fibrosis of heart valves remains limited. This study explored the induction effects of TGF-β۱, IL-۶, TNF-α, and IL-۱β on VICs isolated from New Zealand rabbits (Oryctolagus cuniculus) and established an in vitro model of myofibroblast differentiation, marked by α-smooth muscle actin (α-SMA) expression. A laboratory experiment employing a posttest-only control group design was performed in vitro. VICs were extracted from the heart valves of Oryctolagus cuniculus and later stimulated with (۱) ۱۰ ng/mL IL-۱β, (۲) ۵۰ ng/mL IL-۶, (۳) ۵ ng/mL TGF-β۱, and (۴) ۱۰ ng/mL TNF-α. The expression of α-SMA, observed via immunocytochemistry, was used to indicate the differentiation of VICs into myofibroblasts. Immunochemical staining showed significantly increased myofibroblast differentiation across all intervention groups, with a mean α-SMA expression increase of ۱۲.۷۰ for IL-۱β, ۱۲.۶۴ for IL-۶, ۱۲.۴۸ for TGF-β۱, and ۱۲.۴۸ for TNF-α as opposed to each control group (p < ۰.۰۰۱). No variance in α-SMA concentration was observed among intervention groups. The four tested cytokines had similar effects in inducing the differentiation of VICs into myofibroblast, as expressed by α-SMA. These findings may serve as an in vitro model of valvular fibrosis and encourage further research into inhibiting valve fibrosis caused by RHD.

کلیدواژه ها:

Valvular interstitial cell ، α-smooth muscle actin ، myofibroblast ، RHEUMATIC HEART DISEASE