Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 171, Issue 13, Pages 3115-3131Publisher
WILEY-BLACKWELL
DOI: 10.1111/bph.12677
Keywords
isoprostanes; lipid peroxidation; oxidative stress; cardiovascular disease; TxA2; prostanoid receptor
Categories
Funding
- IZKF Wurzburg [E-251]
- German Research Foundation [DFG Be 3246/4-1, SFB 688]
- Bundesministerium fur Bildung und Forschung through the Comprehensive Heart Failure Center [BMBF01 EO1004]
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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.
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