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Citations to this article

Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension
Mark W. Geraci, … , Rubin M. Tuder, Norbert F. Voelkel
Mark W. Geraci, … , Rubin M. Tuder, Norbert F. Voelkel
Published June 1, 1999
Citation Information: J Clin Invest. 1999;103(11):1509-1515. https://doi.org/10.1172/JCI5911.
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Article

Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension

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Abstract

Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway leading to prostacyclin (PGI2) production. Patients with severe pulmonary hypertension have a PGIS deficiency of their precapillary vessels, but the importance of this deficiency for lung vascular remodeling remains unclear. We hypothesized that selective pulmonary overexpression of PGIS may prevent the development of pulmonary hypertension. To study this hypothesis, transgenic mice were created with selective pulmonary PGIS overexpression using a construct of the 3.7-kb human surfactant protein-C (SP-C) promoter and the rat PGIS cDNA. Transgenic mice (Tg+) and nontransgenic littermates (Tg–) were subjected to a simulated altitude of 17,000 ft for 5 weeks, and right ventricular systolic pressure (RVSP) was measured. Histology was performed on the lungs. The Tg+ mice produced 2-fold more pulmonary 6-keto prostaglandin F1α (PGF1α) levels than did Tg– mice. After exposure to chronic hypobaric hypoxia, Tg+ mice have lower RVSP than do Tg– mice. Histologic examination of the lungs revealed nearly normal arteriolar vessels in the Tg+ mice in comparison with vessel wall hypertrophy in the Tg– mice. These studies demonstrate that Tg+ mice were protected from the development of pulmonary hypertension after exposure to chronic hypobaric hypoxia. We conclude that PGIS plays a major role in modifying the pulmonary vascular response to chronic hypoxia. This has important implications for the pathogenesis and treatment of severe pulmonary hypertension.

Authors

Mark W. Geraci, Bifeng Gao, David C. Shepherd, Mark D. Moore, Jay Y. Westcott, Karen A. Fagan, Lori A. Alger, Rubin M. Tuder, Norbert F. Voelkel

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Total citations by year

Year: 2023 2022 2021 2020 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 Total
Citations: 6 2 5 4 2 3 1 5 3 6 10 13 10 7 8 14 7 6 10 8 13 19 9 1 172
Citation information
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Citations to this article in year 2015 (5)

Title and authors Publication Year
EP3 receptor deficiency attenuates pulmonary hypertension through suppressing Rho/TGFβ1 pathway
Ankang Lu, Caojian Zuo, Yuhu He, Guilin Chen, Lingjuan Piao, Jian Zhang, Bing Xiao, Yujun Shen, Juan Tang, Deping Kong, Sara Alberti, Di Chen, Shenkai Zuo, Qianqian Zhang, Shuai Yan, Xiaochun Fei, Fei Yuan, Bin Zhou, Sheng Zhong Duan, Yu Yu, Michael Lazarus, Yunchao Su, Richard Breyer, Colin Funk, Ying Yu
Journal of Clinical Investigation 2015
The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: Role of membrane versus nuclear receptors
LH Clapp, R Gurung
Prostaglandins & Other Lipid Mediators 2015
Inhaled therapy for the management of perioperative pulmonary hypertension
H Ramakrishna, CA Thunberg, ST Morozowich
Annals of Cardiac Anaesthesia 2015
Pathophysiology and Pharmacotherapy of Cardiovascular Disease
G Jagadeesh, P Balakumar, K Maung-U
2015
Diagnosis and Management of Pulmonary Hypertension
JR Klinger, RP Frantz
2015

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