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G Protein Coupled Receptor 75 and Its Role in Pulmonary Hypertension
Author(s) -
D’Addario Catherine,
Kitagawa Atsushi,
Zhang Frank,
Zeldin Darryl,
Gruzdev Artiom,
Garcia Victor,
Schwartzman Michal,
Gupte Sachin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02325
Subject(s) - hypoxic pulmonary vasoconstriction , ventricle , pulmonary hypertension , medicine , vasoconstriction , hypoxia (environmental) , ventricular pressure , cardiology , pulmonary artery , receptor , endocrinology , blood pressure , oxygen , chemistry , organic chemistry
Pulmonary Hypertension (PH) is a multifactorial disease with poor prognosis and inadequate treatment. Recent studies have shown that the orphan G Protein Coupled Receptor 75 (GPR75) is upregulated in the pulmonary vessels of PH patients, especially in females. Therefore, we hypothesized that GPR75 knock out (GPR75KO) mice will be protected from developing PH. We placed 3‐month‐old female GPR75KO (n=6) and control C57BL/C mice (n=10) in a hypoxic chamber with 10% Oxygen or at atmospheric oxygen for 5 weeks. At the end of 5 weeks, we performed echocardiograms and right heart catheterizations. GPR75KO mice were protected from developing PH (Right Ventricle Systolic Pressure (RVSP) of 26mmHg and Right Ventricle Diastolic Pressure (RVDP) of 2 mmHg), while C57BL/C mice developed PH under hypoxia (RSVP and RDVP of 56mmHg and 12mmHg, respectively). Wire myography was performed on isolated intra‐lobar pulmonary arteries from GPR75KO mice (n=3) and WT mice (n=31). Hypoxic pulmonary vasoconstriction (HPV) was abolished in GPR75KO as compared to WT. HPV response in WT was blocked (P<0.05) by antibody against RANTES (CCL5), a putative GPR75 ligand. These results suggest GPR75 plays a major role in the development of HPV and PH. Support or Funding Information This study was supported by NIH grant 1RO1HL139793 (MLS).