Abstract
Pulmonary arterial hypertension (PAH) is a progressive fatal disease characterized by a vascular remodeling of small pulmonary arteries leading to an increased right ventricular (RV) pressure and ultimately to RV failure. Treatments currently available do not cure the disease and new therapeutic strategies are needed. This involves the use of relevant animal models
The sugen (Su) model combines the administration of a vascular endothelial growth factor receptor blocker to a sequential exposure to hypoxia (Hx) and normoxia (Nx). Unlike the monocrotaline and hypoxia-induced PAH models, animals exposed to SuHxNx develop severe PAH with complex pulmonary vascular changes. However, very little data is available regarding temporal evolution of the disease, especially the appearance of plexiform lesions. The present work aimed at characterizing the progression of the disease over time using different approaches.
Rats were treated with Su, exposed to Hx and maintained in Nx up to 10 weeks. RV pressure and hypertrophy were then measured and histological analysis of small pulmonary arteries was performed.
As expected, treatment with Su associated with an exposure to Hx+Nx worsened Hx-induced PAH (RVSP>70 mmHg) with severe medial hypertrophy and intimal proliferation. The extent of vascular remodeling increased with the duration of Nx to reach a maximum after 3 weeks with 50% of the analysed vessels partially or totally occluded. Finally, plexiform lesions occurred immediately after the end of Hx and affected 35% of the small pulmonary arteries after 3 weeks of Nx. Death also occurred after 5 weeks.
Exposure to Su+Hx with 3 weeks of Nx could provide a relevant model for the development of new treatments for PAH.
- Copyright ©ERS 2015
