Prostacyclin analogs in clinical use in the United States include
epoprostenol, iloprost and treprostinil
. All three are used to treat pulmonary arterial hypertension (PAH), a severe and progressive disease marked by vasoconstriction and smooth muscle cell proliferation of the pulmonary arterioles.
What are the effects of prostacyclin?
Prostacyclin is a prostaglandin produced by both vascular smooth muscle and endothelium that
stimulates vasodilation
, inhibits smooth muscle growth (antiproliferative effects), and inhibits platelet aggregation.
What is the function of prostacyclin?
Prostacyclin
inhibits platelet aggregation by increasing cyclic AMP levels
. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation.
What do Thromboxanes do?
Thromboxane: A substance made by platelets that
causes blood clotting and constriction of blood vessels
. It also encourages platelet aggregation.
What causes prostacyclin?
Prostacyclin is produced in
endothelial cells
, which line the walls of arteries and veins, from prostaglandin H
2
(PGH
2
) by the action of the enzyme prostacyclin synthase.
Is prostacyclin inflammatory?
Prostacyclin as an
Inflammatory Mediator
As described, prostacyclin (PGI
2
) is best known for its regulatory role within the cardiovascular system, where it promotes VSMC relaxation (vasodilatation) and inhibits platelet aggregation (anti-thrombotic). However, it is also an important inflammatory mediator.
Does COX1 produce prostacyclin?
COX1 expressed in endothelial cells drives vascular and circulating prostacyclin with little role for either COX1 in smooth muscle or COX2 in endothelial cells. Endothelial cell COX1 produces an
antithrombotic effect
, but this is masked by platelet COX1-derived thromboxane.
Is aspirin a prostacyclin?
Aspirin acts primarily by interfering with the biosynthesis of cyclic prostanoids: TXA
2
, prostacyclin, and other prostaglandins.
What enzyme makes prostacyclin?
The production of prostacyclin is dependent upon
cyclooxygenase (COX) enzymes
, which convert arachidonic acid into prostaglandin H
2
, the precursor of all prostanoids.
Is iloprost a prostacyclin?
Iloprost is
a stable prostacyclin analog
with a serum half-life of 20 to 25 minutes. Aerosolization of prostacyclin or its stable analog iloprost causes selective pulmonary vasodilatation, increases cardiac output, and improves venous and arterial oxygenation in patients with severe PH.
Where are Thromboxanes found?
Thromboxane-A synthase, an enzyme found in
platelets
, converts the arachidonic acid derivative prostaglandin H
2
to thromboxane.
What do Lipoxins do?
Lipoxins are
endogenous anti-inflammatory, pro-resolving molecules
that play a vital role in reducing excessive tissue injury and chronic inflammation.
Do eicosanoids cause inflammation?
Although eicosanoids are
most frequently associated with inflammation
, they also have homeostatic functions (Box 1).
Does prostacyclin cause bronchodilation?
All of these processes can be modulated by cyclic adenosine monophosphate-elevating prostaglandins E
2
and I
2
(also known as prostacyclin). These prostanoids have long been
known to elicit bronchodilation
and to protect against bronchoconstriction provoked by a variety of stimuli.
What does ADP do to platelets?
ADP not only
causes primary aggregation of platelets
but is also responsible for the secondary aggregation induced by ADP and other agonists. ADP also induces platelet shape change, secretion from storage granules, influx and intracellular mobilization of Ca2+, and inhibition of stimulated adenylyl cyclase activity.
Is prostacyclin an anticoagulant?
Prostacyclin is a platelet inhibitor that can be safely used as an
efficient anticoagulant in CRRT
. When combined with heparin, it induces a heparin-sparing effect, which can reduce the dosage and side effects of heparin.
