Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.

ABSTRACT:

Rationale

Pulmonary hypertension (PH) is a multifactorial disease with a poor prognosis and inadequate treatment options. We found two-fold higher expression of the orphan G-Protein Coupled Receptor 75 (GPR75) in leukocytes and pulmonary arterial smooth muscle cells from idiopathic PH patients and from lungs of C57BL/6 mice exposed to hypoxia. We therefore postulated that GPR75 signaling is critical to the pathogenesis of PH.

Methods

To test this hypothesis, we exposed global (Gpr75^-/-) and endothelial cell (EC) GPR75 knockout (EC-Gpr75^-/-) mice and wild-type (control) mice to hypoxia (10% oxygen) or normal atmospheric oxygen for 5 weeks. We then recorded echocardiograms and performed right heart catheterizations.

Results

Chronic hypoxia increase

SUBMITTER: D'Addario CA 

PROVIDER: S-EPMC10841449 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature