Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation - PubMed (original) (raw)

Review

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation

Jochen Bauer et al. Br J Pharmacol. 2014 Jul.

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.

Keywords: TxA2/prostanoid receptor; cardiovascular disease; isoprostanes; lipid peroxidation; oxidative stress.

© 2014 The British Pharmacological Society.

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Figures

Figure 1

Figure 1

(A) Enzymatic and non-enzymatic formation of PGs and isoprostanes. (B) Non-enzymatic formation of isoprostanes exemplified for 8-_iso_-PGF2α (15-F2t-IsoP, iPF2α -III) and 5-F2t-IsoP (iPF2α -IV). Arachidonic acid (AA) is released from phospholipids by PLA2 and subsequently converted to PGs by COX. Esterified AA is converted non-enzymatically by ROS to phospholipid-bound isoprostanes. The latter being subsequently released as non-esterified congeners.

Figure 2

Figure 2

Isoprostane-mediated signalling via TP receptor activation in ECs associated with endothelial function and homeostasis.

Figure 3

Figure 3

Proposed effects of isoprostanes in the cardiovascular system. Isoprostanes act as partial agonists of the TP receptor and may represent important alternative activators of the TP receptor especially in the context of oxidative stress.

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