Compensatory activation of PI3K/AKT signaling and apoptosis-associated protein expression in pulmonary hypertension-induced right ventricular dysfunction
- 1Department of Pediatric Cardiology Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
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.
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BibTeX
@article{zhang2026compensatory,
title = {{Compensatory activation of PI3K/AKT signaling and apoptosis-associated protein expression in pulmonary hypertension-induced right ventricular dysfunction}},
author = {Han Zhang and Qixu Zhao and Jiashu Sun and Yusong Deng and Guofeng Xing and Weiran Duan and Gang Li and Qiang Wang},
journal = {Experimental and Therapeutic Medicine},
year = {2026},
month = oct,
doi = {10.3892/etm.2026.13342},
url = {https://europepmc.org/article/PMC/PMC13725646},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Compensatory activation of PI3K/AKT signaling and apoptosis-associated protein expression in pulmonary hypertension-induced right ventricular dysfunction
AU - Han Zhang
AU - Qixu Zhao
AU - Jiashu Sun
AU - Yusong Deng
AU - Guofeng Xing
AU - Weiran Duan
AU - Gang Li
AU - Qiang Wang
PY - 2026
DA - 2026/10/23
JO - Experimental and Therapeutic Medicine
DO - 10.3892/etm.2026.13342
UR - https://europepmc.org/article/PMC/PMC13725646
AB - 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.
SN - 1792-0981
SN - 1792-1015
ER -