Animal models of pulmonary arterial hypertension associated with atrial septal defect

Abstract

Abstract Pulmonary arterial hypertension (PAH) is a well-known complication of congenital heart disease (CHD). The lack of a satisfactory animal model for PAH associated with CHD (PAH-CHD) has limited progress in understanding the pathogenesis of PAH and the development of therapeutic agents. The development of a rat model for PAH associated with atrial septal defect (ASD) was achieved through atrial septal puncture and thermal ablation. Two and 4 weeks after modeling, hematoxylin and eosin staining showed that the vascular thickness, vascular thickness index, vascular area, and vascular area index in pulmonary arteries with an outer diameter of 50–300 μm in the PAH-ASD 2 and 4 weeks group were higher than those in the sham group (all P < 0.05). Alpha-smooth muscle actin (ɑ-SMA) staining showed that the medial thickness, medial thickness index, medial area, and medial area index in pulmonary arteries with an outer diameter of 50–300 µm at 2 and 4 weeks after modeling were significantly higher than those in the sham group (all P < 0.05). Additionally, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in the PAH-ASD 2 and 4 weeks groups were significantly higher than those in the sham group (both P < 0.05). Elastin van Gieson staining showed that the vascular obstruction score in the PAH-ASD 2 and 4 weeks group was significantly higher than that in the sham group (both P < 0.05). The PAH-ASD rats were successfully generated. These findings suggest that our model would be useful for further research into the pathogenesis, prevention, and treatment of PAH-ASD.

Keywords

• Animal model
• Pulmonary arterial hypertension
• Atrial septostomy
• Rat