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Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A 2 receptor activation
Author(s) -
Bauer Jochen,
Ripperger Anne,
Frantz Stefan,
Ergün Süleyman,
Schwedhelm Edzard,
Benndorf Ralf A
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12677
Subject(s) - isoprostanes , isoprostane , context (archaeology) , oxidative stress , arachidonic acid , prostanoid , thromboxane a2 , thromboxane receptor , chemistry , thromboxane , lipid peroxidation , endocrinology , receptor , medicine , platelet , biochemistry , biology , enzyme , paleontology
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 T x A 2 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 T x A 2 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.