Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling

Yasushi Hoshikawa, Norbert F. Voelkel, Tracy L. Gesell, Mark D. Moore, Kenneth G. Morris, Lori A. Alger, Shuh Narumiya, Mark W. Geraci

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Prostacyclin (PGI2) reduces pulmonary vascular resistance and attenuates vascular smooth muscle cell proliferation through signal transduction following ligand binding to its receptor. Because patients with severe pulmonary hypertension have a reduced PGI2 receptor (PGI-R) expression in the remodeled pulmonary arterial smooth muscle, we hypothesized that pulmonary vascular remodeling may be modified PGI-R dependently. To test this hypothesis, PGI-R knockout (KO) and wild-type (WT) mice were subjected to a simulated altitude of 17,000 ft or Denver altitude for 3 wk, and right ventricular pressure and lung histology were assessed. The PGI-R KO mice developed more severe pulmonary hypertension and vascular remodeling after chronic hypoxic exposure when compared to the WT mice. Our results indicate that PGI2 and its receptor play an important role in the regulation of hypoxia-induced pulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)314-318
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume164
Issue number2
DOIs
StatePublished - Jul 15 2001

Keywords

  • Chronic hypoxia
  • Knockout mice
  • Prostacyclin receptor
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Hoshikawa, Y., Voelkel, N. F., Gesell, T. L., Moore, M. D., Morris, K. G., Alger, L. A., Narumiya, S., & Geraci, M. W. (2001). Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling. American journal of respiratory and critical care medicine, 164(2), 314-318. https://doi.org/10.1164/ajrccm.164.2.2010150