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Prostacyclin: an inflammatory paradox.

Stitham J, Midgett C, Martin KA, Hwa J - Front Pharmacol (2011)

Bottom Line: In recent years, prostacyclin (PGI(2)) has also been shown to promote differentiation and inhibit proliferation in vascular smooth muscle cells.In addition to these well-described homeostatic roles within the cardiovascular system, prostacyclin (PGI(2)) also plays an important role as an inflammatory mediator.The emerging role of prostacyclin (PGI(2)) in this context provides new opportunities for understanding the complex molecular basis for inflammatory-related diseases, and insights into the development of current and future anti-inflammatory treatments.

View Article: PubMed Central - PubMed

Affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University New Haven, CT, USA.

ABSTRACT
Prostacyclin (PGI(2)) is a member of the prostaglandin family of bioactive lipids. Its best-characterized role is in the cardiovascular system, where it is released by vascular endothelial cells, serving as a potent vasodilator and inhibitor of platelet aggregation. In recent years, prostacyclin (PGI(2)) has also been shown to promote differentiation and inhibit proliferation in vascular smooth muscle cells. In addition to these well-described homeostatic roles within the cardiovascular system, prostacyclin (PGI(2)) also plays an important role as an inflammatory mediator. In this review, we focus on the contribution of prostacyclin (PGI(2)) as both a pathophysiological mediator and therapeutic agent in three major inflammatory-mediated disease processes, namely rheumatoid arthritis, where it promotes disease progression ("pro-inflammatory"), along with pulmonary vascular disease and atherosclerosis, where it inhibits disease progression ("anti-inflammatory"). The emerging role of prostacyclin (PGI(2)) in this context provides new opportunities for understanding the complex molecular basis for inflammatory-related diseases, and insights into the development of current and future anti-inflammatory treatments.

No MeSH data available.


Related in: MedlinePlus

Paradoxical actions of prostacyclin in three inflammatory diseases. Prostacyclin (PGI2) serves as a protective, anti-inflammatory mediator in the processes of atherosclerosis and pulmonary vascular diseases, such as pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). Conversely, in rheumatological conditions, such as rheumatoid arthritis (RA) and osteoarthritis (OA), PGI2 acts as a propagatory, pro-inflammatory molecule.
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Figure 2: Paradoxical actions of prostacyclin in three inflammatory diseases. Prostacyclin (PGI2) serves as a protective, anti-inflammatory mediator in the processes of atherosclerosis and pulmonary vascular diseases, such as pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). Conversely, in rheumatological conditions, such as rheumatoid arthritis (RA) and osteoarthritis (OA), PGI2 acts as a propagatory, pro-inflammatory molecule.

Mentions: As described, prostacyclin (PGI2) 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. The seminal work by Vane (1971) demonstrating the inhibition of prostaglandin biosynthesis as the mechanism of action for aspirin (acetylsalicylic acid) and other aspirin-like drugs first highlighted the importance of the prostaglandin family of molecules, and set the stage for the development of many pharmacologic agents, such as traditional, non-selective non-steroidal anti-inflammatory drugs (tNSAIDs) and the newer selective COX-2 inhibitors. Further work by Davies et al. (1984) pinpointed particular prostaglandins, principally prostaglandin E2 (PGE2) and prostacyclin (PGI2), in the mediation of vascular permeability associated with the hyperemia and edema seen with acute inflammation. Murata et al. (1997) demonstrated the involvement of prostacyclin (PGI2)-mediated inflammatory swelling in vivo, using prostacyclin receptor deficient (IP−/−) mice. In these critical experiments, it was shown that mice lacking the prostacyclin receptor had a reduced inflammatory response, as measured by percent change in vascular permeability using a carrageenan-induced paw-edema model (Murata et al., 1997). Limb edema was decreased by approximately 50% in IP-deficient mice, similar to levels seen in mice pre-treated with the non-steroidal anti-inflammatory agent indomethacin. Moreover, a significant reduction in lung exudate volume, using a carrageenan-induced pleurisy model, was also observed (although data not shown) for IP-deficient mice as well (Murata et al., 1997). In contrast, a study by Takahashi et al. (2002) demonstrated the IP-deficient mice showed higher skin and airway immune responses (relating to increased capillary permeability in these tissues) in antigen-sensitized inflammation, suggesting a protective role for PGI2 in allergic inflammation. These studies (among others) have highlighted prostacyclin as a major endogenous mediator of inflammation – both pro-inflammatory and anti-inflammatory, depending upon the tissue and pathological model being studied (Figure 2).


Prostacyclin: an inflammatory paradox.

Stitham J, Midgett C, Martin KA, Hwa J - Front Pharmacol (2011)

Paradoxical actions of prostacyclin in three inflammatory diseases. Prostacyclin (PGI2) serves as a protective, anti-inflammatory mediator in the processes of atherosclerosis and pulmonary vascular diseases, such as pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). Conversely, in rheumatological conditions, such as rheumatoid arthritis (RA) and osteoarthritis (OA), PGI2 acts as a propagatory, pro-inflammatory molecule.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108482&req=5

Figure 2: Paradoxical actions of prostacyclin in three inflammatory diseases. Prostacyclin (PGI2) serves as a protective, anti-inflammatory mediator in the processes of atherosclerosis and pulmonary vascular diseases, such as pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). Conversely, in rheumatological conditions, such as rheumatoid arthritis (RA) and osteoarthritis (OA), PGI2 acts as a propagatory, pro-inflammatory molecule.
Mentions: As described, prostacyclin (PGI2) 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. The seminal work by Vane (1971) demonstrating the inhibition of prostaglandin biosynthesis as the mechanism of action for aspirin (acetylsalicylic acid) and other aspirin-like drugs first highlighted the importance of the prostaglandin family of molecules, and set the stage for the development of many pharmacologic agents, such as traditional, non-selective non-steroidal anti-inflammatory drugs (tNSAIDs) and the newer selective COX-2 inhibitors. Further work by Davies et al. (1984) pinpointed particular prostaglandins, principally prostaglandin E2 (PGE2) and prostacyclin (PGI2), in the mediation of vascular permeability associated with the hyperemia and edema seen with acute inflammation. Murata et al. (1997) demonstrated the involvement of prostacyclin (PGI2)-mediated inflammatory swelling in vivo, using prostacyclin receptor deficient (IP−/−) mice. In these critical experiments, it was shown that mice lacking the prostacyclin receptor had a reduced inflammatory response, as measured by percent change in vascular permeability using a carrageenan-induced paw-edema model (Murata et al., 1997). Limb edema was decreased by approximately 50% in IP-deficient mice, similar to levels seen in mice pre-treated with the non-steroidal anti-inflammatory agent indomethacin. Moreover, a significant reduction in lung exudate volume, using a carrageenan-induced pleurisy model, was also observed (although data not shown) for IP-deficient mice as well (Murata et al., 1997). In contrast, a study by Takahashi et al. (2002) demonstrated the IP-deficient mice showed higher skin and airway immune responses (relating to increased capillary permeability in these tissues) in antigen-sensitized inflammation, suggesting a protective role for PGI2 in allergic inflammation. These studies (among others) have highlighted prostacyclin as a major endogenous mediator of inflammation – both pro-inflammatory and anti-inflammatory, depending upon the tissue and pathological model being studied (Figure 2).

Bottom Line: In recent years, prostacyclin (PGI(2)) has also been shown to promote differentiation and inhibit proliferation in vascular smooth muscle cells.In addition to these well-described homeostatic roles within the cardiovascular system, prostacyclin (PGI(2)) also plays an important role as an inflammatory mediator.The emerging role of prostacyclin (PGI(2)) in this context provides new opportunities for understanding the complex molecular basis for inflammatory-related diseases, and insights into the development of current and future anti-inflammatory treatments.

View Article: PubMed Central - PubMed

Affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University New Haven, CT, USA.

ABSTRACT
Prostacyclin (PGI(2)) is a member of the prostaglandin family of bioactive lipids. Its best-characterized role is in the cardiovascular system, where it is released by vascular endothelial cells, serving as a potent vasodilator and inhibitor of platelet aggregation. In recent years, prostacyclin (PGI(2)) has also been shown to promote differentiation and inhibit proliferation in vascular smooth muscle cells. In addition to these well-described homeostatic roles within the cardiovascular system, prostacyclin (PGI(2)) also plays an important role as an inflammatory mediator. In this review, we focus on the contribution of prostacyclin (PGI(2)) as both a pathophysiological mediator and therapeutic agent in three major inflammatory-mediated disease processes, namely rheumatoid arthritis, where it promotes disease progression ("pro-inflammatory"), along with pulmonary vascular disease and atherosclerosis, where it inhibits disease progression ("anti-inflammatory"). The emerging role of prostacyclin (PGI(2)) in this context provides new opportunities for understanding the complex molecular basis for inflammatory-related diseases, and insights into the development of current and future anti-inflammatory treatments.

No MeSH data available.


Related in: MedlinePlus