Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock. Export

@article{citeulike:1971218, abstract = {Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR-gamma 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-gamma 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-gamma ligands reach far beyond their use as insulin sensitizers. Recently, PPAR-gamma has been implicated as a regulator of cellular inflammatory and ischemic responses. PPAR-gamma 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-gamma-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-gamma, as well as the potential therapeutic effects of PPAR-gamma agonists in animal models of ischemia/reperfusion, inflammation and shock.}, address = {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.}, author = {Abdelrahman, M. and Sivarajah, A. and Thiemermann, C.}, citeulike-article-id = {1971218}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cardiores.2004.12.008}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15721857}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15721857}, day = {1}, doi = {10.1016/j.cardiores.2004.12.008}, issn = {0008-6363}, journal = {Cardiovasc Res}, keywords = {inflammation, ischemia-reperfusion, ppar-gamma, shock}, month = {March}, number = {4}, pages = {772--781}, posted-at = {2009-01-11 13:28:34}, priority = {3}, title = {Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock.}, url = {http://dx.doi.org/10.1016/j.cardiores.2004.12.008}, volume = {65}, year = {2005} }

TY - JOUR ID - citeulike:1971218 L3 - citeulike-article-id:1971218 N2 - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR-gamma 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-gamma 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-gamma ligands reach far beyond their use as insulin sensitizers. Recently, PPAR-gamma has been implicated as a regulator of cellular inflammatory and ischemic responses. PPAR-gamma 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-gamma-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-gamma, as well as the potential therapeutic effects of PPAR-gamma agonists in animal models of ischemia/reperfusion, inflammation and shock. IS - 4 JF - Cardiovasc Res SN - 0008-6363 AD - 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. EP - 781 TI - Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock. VL - 65 SP - 772 KW - inflammation KW - ischemia-reperfusion KW - ppar-gamma KW - shock AU - Abdelrahman, M AU - Sivarajah, A AU - Thiemermann, C PY - 2005/03/01/ UR - http://dx.doi.org/10.1016/j.cardiores.2004.12.008 ER -