The role of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway in the pulmonary vascular remodeling of pulmonary arterial hypertension in rats

Abstract

: This study aimed to investigate the role of the phosphatidylinositol 3-kinase / protein kinase B (PI3K / Akt) signaling pathway in the pulmonary vascular remodeling (PVR) of pulmonary arterial hypertension (PAH) in rats. A PAH model in rats was established through a left pneumonectomy and monocrotaline (MCT) injection, using the transglutaminase 2 (TG2) inhibitor cystamine dihydrochloride for intervention. Thirty healthy male Sprague Dawley rats were randomized into a control group, a model group, and an intervention group ( n = 10 for each group). The mean pulmonary arterial pressure (mPAP) was measured in all groups after 35 days, and the right ventricular hypertrophy index (RVHI) was calculated. Hematoxylin and eosin and lung elastic-fiber staining were used on the rats’ lung tissue in all three groups. The changes in pulmonary blood vessels and lung tissue force and the percentage of medial hypertrophy of small pulmonary arteries (WT%), vessel wall area to total area ratio (WA%), and the neointimal proliferation degree were observed. The Akt messenger RNA (mRNA) expression levels of lung tissues in all three groups were measured using a real-time polymerase chain reaction (RT-PCR) assay, and the protein expression levels of Akt and phosphorylated Akt (p-Akt) in all three groups were measured using a Western blot assay. The results indicated that the PI3K / Akt signaling pathway might play a substantial role in inhibiting pulmonary vascular remodeling (PVR) following intervention with a TG2 inhibitor.