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The mechanistic basis for prostacyclin action in pulmonary hypertension

Clapp, LH; Patel, J; (2010) The mechanistic basis for prostacyclin action in pulmonary hypertension. [Review]. International Journal of Respiratory Care , 6 (1) pp. 27-33. Green open access

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Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries in which patients suffer from elevated pulmonary arterial pressure, right ventricular failure and a reduction in gas exchange. Left untreated the median survival from diagnosis is ~2.8 years, though outcome is significantly worse if patients have underlying pulmonary fibrosis or scleroderma. Injury to the endothelium probably initiates the disease process, with increased production of vasoconstrictors (endothelin and thromboxane) and growth factors accompanying the loss of vasodilator and anti-platelet agents, prostacyclin and nitric oxide, which results in vascular remodelling. To date prostacyclin therapy still remains the most efficacious treatment for PAH, although its short half-life and cumbersome delivery (continuous infusion) meant analogues with improved stability and alternative routes of delivery were developed. Classically, prostacyclin agents are thought to produce haemodynamic and anti-proliferative effects through prostacyclin (IP) receptors coupled to cyclic AMP generation, though other prostanoid receptors may contribute (EP2, EP4) or counterbalance (EP1, EP3) these responses. Increasing evidence suggests peroxisome proliferator-activated receptors (PPARs) are also cellular targets for prostacyclin agonists, regulating cell growth, inflammation and apoptosis through these transcription factors. Activation involves ligand binding and/or membrane receptors but probably not cyclic AMP. Here we discuss recent advances in our understanding of PPARs and how they may represent an important therapeutic target in PAH

Type: Article
Title: The mechanistic basis for prostacyclin action in pulmonary hypertension
Location: UK
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/1508531
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