Increased plasma levels of 15-deoxyDelta prostaglandin J2 are associated with good outcome in acute atherothrombotic ischemic stroke.

Abstract

BACKGROUND AND PURPOSE:

The 15-deoxyDelta prostaglandin J2 (15-dPGJ2) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor-gamma (PPARgamma), a nuclear receptor that can exert potent anti-inflammatory actions by repressing inflammatory genes when activated. It has been suggested that 15-dPGJ2 could be beneficial in neurological disorders in which inflammation contributes to cell death such as stroke.

METHODS:

We investigated the relationship between plasma levels of 15-dPGJ2 and early neurological deterioration (END), infarct volume, and neurologic outcome in 552 patients with an acute stroke admitted within 24 hours after symptoms onset.

RESULTS:

Median [quartiles] plasma 15-dPGJ2 levels on admission were significantly higher in patients than in controls (60.5 [11.2 to 109.4] versus 5.0 [3.8 to 7.2] pg/mL; P<0.0001). Levels of this prostaglandin were also significantly higher in patients with vascular risk factors (history of hypertension or diabetes) and with atherothrombotic infarcts (113.9 [81.6 to 139.7] pg/mL), than in those with lacunar (58.7 [32.7 to 86.2] pg/mL), cardioembolic (12.1 [6.5 to 39.2] pg/mL), or undetermined origin infarcts (11.4 [5.6 to 24.3] pg/mL) (P<0.0001). In the subgroup of patients with atherothrombotic infarcts, the adjusted odds ratio of END and poor outcome for 1 pg/mL increase in 15-dPGJ2 were 0.95 (95% CI, 0.94 to 0.97) and 0.97 (95% CI, 0.96 to 0.98), respectively. In a generalized linear model, by 1 U increase in 15-dPGJ2, there was a reduction of 0.47 mL (95% CI, 0.32 to 0.63) in the mean estimated infarct volume.

CONCLUSIONS:

Increased plasma 15-dPGJ2 concentration is associated with good early and late neurological outcome and smaller infarct volume. These findings suggest a neuroprotective effect of 15-dPGJ2 in atherothrombotic ischemic stroke.

• Authors: Miguel Blanco, María Angeles Moro, Antonio Dávalos, Rogelio Leira, Mar Castellanos, Joaquín Serena, José Vivancos, Manuel Rodríguez-Yáñez, Ignacio Lizasoain, José Castillo
• Journal: Stroke (Stroke) Vol. 36 Issue 6 Pg. 1189-94 (Jun 2005) ISSN: 1524-4628 [Electronic] United States
• PMID: 15879329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxyprostaglandin J2
• Anti-Inflammatory Agents
• Ligands
• PPAR gamma
• Prostaglandin D2

Topics

• Acute Disease
• Aged
• Anti-Inflammatory Agents (pharmacology)
• Brain Ischemia (pathology)
• Case-Control Studies
• Female
• Humans
• Inflammation
• Ligands
• Male
• Middle Aged
• Nervous System Diseases (pathology)
• Odds Ratio
• PPAR gamma (agonists, metabolism)
• Prostaglandin D2 (analogs & derivatives, blood)
• Regression Analysis
• Stroke (blood, mortality, therapy)
• Thrombosis (blood, mortality, therapy)
• Time Factors
• Treatment Outcome