Prostacyclin In PAH
Prostacyclin: A fundamental pathway in PAH
In pulmonary arterial hypertension (PAH), prostacyclin and nitric oxide levels are decreased, and endothelin levels are increased.7 Reduced levels of prostacyclin synthase are found in patients with idiopathic pulmonary arterial hypertension (IPAH).8 Based on animal data, imbalances in prostacyclin and endothelin levels have been implicated in the following:
The clinical significance of prostacyclin deficit in humans is unknown. Animal data cannot imply a benefit in humans.
|"Importantly, the pathways interact, modulating the effect of any single pathway." — McLaughlin and McGoon14|
The prostacyclin pathway is a key treatment target in PAH.
- The absence of prostacyclin has been implicated as a key pathological feature of PAH7
- The addition of prostacyclin has been shown to play a critical role in the management of PAH9,12
- The interplay between the prostacyclin, nitric oxide, and endothelin pathways may have important treatment implications14
Frequency of positive PGI2 synthase (prostacyclin) expression in IPAH and normal lungs8
Frequency of positive PGI2 S expression in lungs of normal patients (n=7) and in patients with IPAH (n=12). Results shown are the mean percentages of positive vessels (p=0.015 for normal versus IPAH small vessels, and p=0.03 for normal versus IPAH medium-sized vessels; p=NS for normal versus PAH large vessels8).
Ventavis cellular effects
4-hour elevation of cAMP levels following single inhaled dose of Ventavis in 10 healthy adults7
Cyclic adenosine monophosphate (cAMP) is the main mediator of the vasodilatory and antiproliferative effects of prostacyclin analogs.16,17 Prostacyclin acts through activation of the cAMP-dependent pathways.7
The association between increased plasma cAMP levels and clinical outcomes in PAH has not been established.