Copyright © 2004, European Society of Cardiology
Beneficial effects of PPAR-
ligands in ischemia–reperfusion injury, inflammation and shock
Centre for Experimental Medicine, Nephrology and Critical Care, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK
* Corresponding author. Tel.: +44 207 882 6118; fax: +44 207 251 1685. Email address: c.thiemermann{at}qmul.ac.uk
Peroxisome proliferator-activated receptor-
(PPAR-) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR- regulates gene expression by forming a heterodimer with the retinoid X receptor (RXR) before binding to sequence-specific PPAR response elements (PPREs) in the promoter region of target genes, thereby regulating several metabolic pathways, including lipid biosynthesis and glucose metabolism. Thiazolidinediones (TZDs, i.e. rosiglitazone, pioglitazone), which are synthetic PPAR- agonists, act as insulin sensitizers and are used in the treatment of type 2 diabetes. In the last few years, it has, however, become evident that the therapeutic effects of PPAR- ligands reach far beyond their use as insulin sensitizers. Recently, PPAR- has been implicated as a regulator of cellular inflammatory and ischemic responses. PPAR- agonists may exert their anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes induced during macrophage differentiation and activation, by either PPAR--dependent or -independent mechanisms. Several lines of evidence suggest that TZDs protect the heart and other organs against the tissue injury caused by ischemia/reperfusion (I/R) injury and shock. This review discusses the anti-inflammatory signalling pathways activated by PPAR-, as well as the potential therapeutic effects of PPAR- agonists in animal models of ischemia/reperfusion, inflammation and shock.
KEYWORDS PPAR-; Regional myocardial infarction; Inflammation; Ischemia; Reperfusion; Shock
Time for primary review 20 days
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