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Review
. 2012 Dec 1;21(126):321-7.
doi: 10.1183/09059180.00004812.

Pathways in pulmonary arterial hypertension: the future is here

Olivier Sitbon  1 , Nicholasw Morrell
Affiliations
Review

Pathways in pulmonary arterial hypertension: the future is here

Olivier Sitbon et al. Eur Respir Rev. .

Abstract

It is well established that the endothelin, nitric oxide and prostacyclin pathways play an important role in the development of pulmonary arterial hypertension (PAH). Indeed, the therapeutic options currently available for the management of PAH all act on one of these mechanistic pathways. However, this is an exciting time for both clinicians and scientists, as increased understanding of the mechanisms involved in the pathogenesis and progression of PAH has resulted in the development of a number of novel therapeutic options. This article highlights how the introduction of new compounds such as macitentan, riociguat and selexipag, which act on the endothelin, nitric oxide and prostacyclin pathways, respectively, have the potential to further improve the prognosis for patients with PAH.

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Conflict of interest statement

Statement of Interest

J-L. Vachiéry has served as a consultant and advisory board member for Actelion, GSK and United Therapeutics. He has received speaker fees from Actelion, Bayer Shering, GSK, Eli Lilly, Pfizer and United Therapeutics. S. Gaine has served as a consultant, advisory board member and has received speaker fees from Actelion, GSK, Pfizer and United Therapeutics.

Figures

Figure 1.
Figure 1.
Key pathways involved in the pathogenesis of pulmonary arterial hypertension: a) endothelin (ET) pathway; b) nitric oxide pathway; and c) prostacyclin (PGI2) pathway. ERA: ET receptor antagonist; ETA/ETB: ET receptor subtypes A and B; SMCs: smooth muscle cells; cGMP: cyclic guanosine monophosphate (GMP); PDE-5: phosphodiesterase type-5; PDE-5i: PDE-5 inhibitor; cAMP: cyclic adenosine monophosphate. Reproduced from [2] with permission from the publisher.
Figure 2.
Figure 2.
Endothelin (ET)-1 plays an important role in vascular remodelling. PAH: pulmonary arterial hypertension; ETA/ETB: ET receptor subtypes A and B; NO: nitric oxide; PGI2: prostacyclin; TXA2: thromboxane A2.
Figure 3.
Figure 3.
Effect of macitentan on survival in a monocrotaline (MCT) rat model of pulmonary hypertension. p=0.002. Reproduced from [15] with permission from the publisher.
See this image and copyright information in PMC

References

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