Aims
Our previous study has indicated that activation of PPAR-纬 inhibits the pro
liferation of rat pulmonary artery smooth muscle cells (PASMCs) in vitro through inducing the expression of heme oxygenase-1 (HO-1), which in turn up-regulates the p21
WAF1 expression. In the present study, we intended to determine whether similar mechanisms have been involved in activation of PPAR-纬 inhibition of development of rat PAH model.
Material and methods
Rat pulmonary arterial hypertension (PAH) model was established by subcutaneous injection of monocrotaline (MCT). Rosiglitazone was administered to activate PPAR-纬. Zinc protoporphyria IX (ZnPP-IX), was used to confirm the role of HO-1 in mediating PPAR-纬 function. Parameters including the right ventricle systolic pressure (RVSP), the right ventricular hypertrophy (RVH) and the percentage of medial wall thickness were used to evaluate the development of PAH. Immunoblotting was used to determine the expression of HO-1 and p21WAF1.
Key findings
Rosiglitazone significantly decreased the RVSP and inhibited the RVH in MCT-induced rat PAH model, and partially inhibited the pulmonary vascular remodeling. These effects were coupled with the sequential increase of HO-1 and p21WAF1 expressions by rosiglitazone.
Significance
Activation of PPAR-纬 benefits PAH by inhibiting proliferation of PASMCs and reducing pulmonary vascular remodeling. The present study suggests that enhancing PPAR-纬 activity might have potential value in clinical treatment of PAH.
