دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.
المؤلفون: D'Addario CA; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Matsumura S; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Kitagawa A; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Lainer GM; Department of Cardiology, and Heart and Vascular Institute, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USA., Zhang F; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., D'silva M; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Khan MY; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Froogh G; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Gruzdev A; National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA., Zeldin DC; National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA., Schwartzman ML; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA., Gupte SA; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. Electronic address: s_gupte@nymc.edu.
المصدر: Vascular pharmacology [Vascul Pharmacol] 2023 Dec; Vol. 153, pp. 107235. Date of Electronic Publication: 2023 Sep 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3649 (Electronic) Linking ISSN: 15371891 NLM ISO Abbreviation: Vascul Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Elsevier Science, c2002-
مواضيع طبية MeSH: Hypertension, Pulmonary*/genetics , Hypertension, Pulmonary*/pathology, Humans ; Mice ; Animals ; Pulmonary Artery ; Ligands ; Cells, Cultured ; Mice, Inbred C57BL ; Hypoxia/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Oxygen/metabolism ; Mice, Knockout
مستخلص: 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 increased right ventricular systolic and diastolic pressures in wild-type mice but not Gpr75 -/- or EC-Gpr75 -/- mice. In situ hybridization and qPCR results revealed that Gpr75 expression was increased in the alveoli, airways and pulmonary arteries of mice exposed to hypoxia. In addition, levels of chemokine (CC motif) ligand 5 (CCL5), a low affinity ligand of GPR75, were increased in the lungs of wild-type, but not Gpr75 -/- , mice exposed to hypoxia, and CCL5 enhanced hypoxia-induced contraction of intra-lobar pulmonary arteries in a GPR75-dependent manner. Gpr75 knockout also increased pulmonary cAMP levels and decreased contraction of intra-lobar pulmonary arteries evoked by endothelin-1 or U46619 in cAMP-protein kinase A-dependent manner.
Conclusion: These results suggest GPR75 has a significant role in the development of hypoxia-induced PH.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 HL166546 United States HL NHLBI NIH HHS; Z01 ES025034 United States ImNIH Intramural NIH HHS; R01 HL132574 United States HL NHLBI NIH HHS; R01 HL168056 United States HL NHLBI NIH HHS; R01 HL139793 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Human; Hypertrophy; Hypoxia; Mice; Pulmonary pressure; Remodeling
المشرفين على المادة: 0 (Ligands)
0 (Receptors, G-Protein-Coupled)
S88TT14065 (Oxygen)
0 (GPR75 protein, human)
تواريخ الأحداث: Date Created: 20230924 Date Completed: 20231216 Latest Revision: 20240430
رمز التحديث: 20240430
مُعرف محوري في PubMed: PMC10841449
DOI: 10.1016/j.vph.2023.107235
PMID: 37742819
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-3649
DOI:10.1016/j.vph.2023.107235