Compensatory activation of PI3K/AKT signaling and apoptosis-associated protein expression in pulmonary hypertension‑induced right ventricular dysfunction
Year: 2026
Type: article
Abstract: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder marked by increased pulmonary vascular resistance and poor prognosis. Right ventricular (RV) dysfunction is the principal determinant of mortality in patients with PH; however, the role of the PI3K/AKT pathway in PH-induced RV remodeling remains poorly defined. The present study generated a hypobaric hypoxia-induced PH model in C57BL/6J mice. Echocardiography, histology, reverse transcription-quantitative PCR, western blotting and immunofluorescence staining were employed to assess RV structure, apoptosis-associated protein expression and fibrosis, while RNA sequencing was used to identify enriched signaling pathways. In parallel, H9C2 cardiomyocytes were treated with angiotensin II (Ang II) with or without the PI3K inhibitor LY294002 to evaluate apoptosis-associated protein expression changes. PH model mice developed RV dysfunction characterized by increased Bax and decreased Bcl-2 expression, accompanied by fibrosis. Transcriptomic analysis revealed significant enrichment of the PI3K/AKT pathway in RV tissues from PH model mice compared with control mice. Pharmacological inhibition of PI3K/AKT signaling with LY294002 further upregulated Bax and downregulated Bcl-2 in Ang II-treated H9C2 cells. In conclusion, PI3K/AKT pathway enrichment may represent a compensatory but insufficient response during PH-induced RV remodeling, and its precise modulation may offer a potential therapeutic strategy for PH-associated RV failure.
Institutions: Capital Medical University, Beijing Anzhen Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223306056