Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010;37(4):391-9.

Prostacyclin therapy for pulmonary arterial hypertension

Cheng-Huai Ruan  1 , Richard A F Dixon, James T Willerson, Ke-He Ruan
Affiliations
Review

Prostacyclin therapy for pulmonary arterial hypertension

Cheng-Huai Ruan et al. Tex Heart Inst J. 2010.

Abstract

In pulmonary arterial hypertension, the blood vessels that carry blood between the heart and lungs are constricted, making it difficult for the heart to pump blood through the lungs. Prostacyclin, a prostanoid metabolized from endogenous arachidonic acid through the cyclooxygenase (COX) pathway, is a potent vasodilator that has been identified as one of the most effective drugs for the treatment of pulmonary arterial hypertension. Currently, prostacyclin and its analogues are widely used in the clinical management of pulmonary arterial hypertension patients. However, the mortality rate associated with pulmonary arterial hypertension has not been significantly reduced within the past 5 years. More powerful therapeutic approaches are needed. This article briefly reviews the current management of pulmonary arterial hypertension to identify the problems associated with present therapies; then it focuses on the emerging technology of prostacyclin synthase gene therapy and cell-based therapy using native stem cells and engineered stem cells with enhanced prostacyclin production capacity. By using the recent advances in technology and the molecular understanding of prostacyclin synthesis, researchers are prepared to make significant advances in the treatment of pulmonary arterial hypertension.

Keywords: Antihypertensive agents; cell therapy; gene therapy; genetic predisposition to disease; hypertension, pulmonary/classification/drug therapy/etiology/genetics; hypertrophy, right ventricular; monocrotaline; prostacyclin; prostacyclin synthetase; pulmonary artery/physiopathology; receptors, endothelin/antagonists & inhibitors; vascular diseases/drug therapy; vasodilator agents.

PubMed Disclaimer

Figures

None
Fig. 1. Models of the newly created fusion (hybrid) enzymes designed to specifically increase prostacyclin production in cells. The fusion enzymes were created by linking COX-1 to PGIS (A), or COX-2 to PGIS (B), respectively, through an optimized TM linker (10 amino acid residues) without alteration of the protein topologies in the endoplasmic reticulum membrane. The direct conversion of arachidonic acid into prostacyclin by the fusion enzyme (through 3 catalytic reactions) is shown. AA = arachidonic acid; COX = cyclooxygenase; PAH = pulmonary arterial hypertension; PGG2 = prostaglandin-G2; PGH2 = prostaglandin-H2; PGIS = prostacyclin synthase; PGI2 = prostacyclin; TM = transmembrane
See this image and copyright information in PMC

References

    1. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54(1 Suppl):S43–54. - PubMed
    1. Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, et al. A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 2009; 119(17): 2313–22. - PMC - PubMed
    1. Burger CD. Pulmonary hypertension in COPD: a review and consideration of the role of arterial vasodilators. COPD 2009;6(2):137–44. - PubMed
    1. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 2009;53(17):1573–619. - PubMed
    1. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association [published erratum appears in Circulation 2009;120(2):e13]. Circulation 2009;119(16):2250–94. - PubMed

MeSH terms