The P4HA1/HIF1α feedback loop modulates endothelial dysfunction in pulmonary hypertension.

ABSTRACT:

Background

Pulmonary hypertension is a severe vascular disease characterised by pulmonary arterial remodeling and right heart failure. However, the role of the glycolytic protein P4HA1 in its pathogenesis remains elusive.

Methods

RNA-seq analysis was performed on hypoxic human pulmonary artery endothelial cells, and P4HA1 expression was validated in PH animal models. In vitro, P4HA1 knockdown was used to assess its effects on glycolysis, proliferation, and migration. Mechanistic studies included HIF1α transcriptional regulation and P4HA1-mediated HIF1α stabilization via reduced ubiquitination. AAV9-shP4HA1 was employed to assess P4HA1's function in pulmonary vascular remodeling in vivo.

Results

P4HA1 was significantly upregulated in human pulmonary arterial endothelia

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12751831 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature