LAUSR

Pulmonary arterial hypertension (PAH) is a fatal syndrome resulting from enhanced pulmonary arterial pressure and pulmonary vessel resistance. Perivascular inflammation and extracellular matrix deposition are considered to be the crucial pathophysiologic bases of PAH. Formononetin (FMN), a natural phytoestrogen isolated from red clover (Trifolium pratense), has a variety of proapoptotic, anti-inflammatory and anti-tumor activities. However, the therapeutic effectiveness of FMN for PAH remains unclear. In the present study, 60 mg/kg monocrotaline (MCT) was first used to induce PAH in rats, and then all rats were treated with different concentrations of FMN (10, 30 and 60 mg/kg/day). At the end of this study, the hemodynamics and pulmonary vascular morphology of rats were evaluated. Specifically, matrix metalloproteinase (MMP)2, transforming growth factor β1 (TGFβ1) and MMP9 were measured using western blot and immunohistochemical staining. Collagen type I, collagen type III, fibronectin, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, ERK and NF-κB were quantified using western blotting. The results demonstrated that FMN significantly alleviated the changes of hemodynamics and pulmonary vascular morphology, and decreased the MCT-induced upregulations of TGFβ1, MMP2 and MMP9 expression levels. Meanwhile, the expression levels of collagen type I, collagen type III and fibronectin in rat lungs decreased after FMN treatment. Furthermore, the phosphorylated ERK and NF-κB also decreased after FMN treatment. Taken together, the present study indicated that FMN serves a therapeutic role in the MCT-induced PAH in rats via suppressing pulmonary vascular remodeling, which may be partially related to ERK and NF-κB signals.