title: Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation.
abstract: Isoprostanes are free radical-catalysed PG-like products of unsaturated fatty acids, such as arachidonic acid, which are widely recognized as reliable markers of systemic lipid peroxidation and oxidative stress in vivo. Moreover, activation of enzymes, such as COX-2, may contribute to isoprostane formation. Indeed, formation of isoprostanes is considerably increased in various diseases which have been linked to oxidative stress, such as cardiovascular disease (CVD), and may predict the atherosclerotic burden and the risk of cardiovascular complications in the latter patients. In addition, several isoprostanes may directly contribute to the functional consequences of oxidant stress via activation of the TxA2 prostanoid receptor (TP), for example, by affecting endothelial cell function and regeneration, vascular tone, haemostasis and ischaemia/reperfusion injury. In this context, experimental and clinical data suggest that selected isoprostanes may represent important alternative activators of the TP receptor when endogenous TxA2 levels are low, for example, in aspirin-treated individuals with CVD. In this review, we will summarize the current understanding of isoprostane formation, biochemistry and (patho) physiology in the cardiovascular context.
authors.affiliation: Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Bauer
authors.forename: Anne
authors.initials: A
authors.lastname: Ripperger
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Benndorf
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002319:Cardiovascular System / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005609:Free Radicals; D028421:Isoprostanes; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2
keywords: TxA2/prostanoid receptor; cardiovascular disease; isoprostanes; lipid peroxidation; oxidative stress