WITHDRAWN: Cyclooxygenase and prostaglandin synthases in atherosclerosis: Recent insights and future perspectives.

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes.

Objective: Receptor for advanced glycation end products (AGEs) (RAGE) plays a central role in the process of plaque rupture in diabetic patients. Recently, it has been reported that RAGE may be downregulated by improving glycemic control. In contrast, despite being well known that RAGE may be induced in human vessels in a glucose-independent fashion, also by myeloperoxidase (MPO)-dependent AGE generation, no data exist regarding the possibility of a pharmacological modulation of glucose-independent RAGE generation.

COX-2 and atherosclerosis.

Inflammation plays a central role in the development of atherosclerotic disease, from the early phases of lesion formation to plaque disruption, the main underlying cause of acute ischemic syndromes. Arachidonic acid metabolism is implicated in the pathophysiology of ischemic syndromes affecting the coronary or cerebrovascular territory, as demonstrated by biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. In particular, much attention has been focused on the pathway catalyzed by cyclooxygenase (COX), which leads to the generation of a variety of lipid mediators known as prostanoids.

Cyclooxygenase-2 inhibition: vascular inflammation and cardiovascular risk.

The inducible isoform of cyclooxygenase-2 (COX-2) plays a role in pathophysiologic processes like inflammation and pain but is also constitutively expressed in tissues such as the kidney or vascular endothelium, where it exerts important physiologic functions. Although much evidence exists that implicates COX-2 in atherosclerosis, its role in this setting remains substantially uncertain. This observation is also confirmed by the results of clinical trials of selective COX-2 inhibitors.

Role of angiotensin II receptor blockers in atherosclerotic plaque stability.

Several clinical trials have shown that agents blocking the renin-angiotensin system reduce the incidence of acute ischaemic events. This effect was independent from blood pressure reduction and was presumably related to plaque stabilisation. With the aim of investigating potential mechanisms underlying this effect, carotid plaques were analysed in a recent study from patients randomised to treatment with the angiotensin receptor blocker irbesartan, or the diuretic chlorthalidone for 4 months before carotid endarterectomy.

Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human.

Objective: We recently demonstrated that inducible cyclooxygenase/PGE synthase-1 (COX-2/mPGES-1) are overexpressed in symptomatic plaques in association with PGE2-dependent metalloproteinase (matrix metalloproteinase [MMP]) biosynthesis and plaque rupture. However, it is not known which of the 4 PGE2 receptors (EP1-4) mediates macrophage metalloproteinase generation. The aim of this study was to characterize EP1-4 expression in plaques from symptomatic and asymptomatic patients undergoing carotid endarterectomy and correlate it with the extent of inflammatory infiltration, COX-2/mPGES-1 and MMP expression and clinical features of patients' presentation.

Association between 5-lipoxygenase expression and plaque instability in humans.

Objective: The participation of 5-lipoxygenase (5-LO) in the development of atherosclerosis has been suggested by recent studies. However, a role for 5-LO as a modulator of atherosclerotic plaque instability has not been previously reported in humans. Thus, the aims of this study was to analyze the expression of 5-LO in human carotid plaques and to investigate the mechanism by which this enzyme could lead to plaque instability and rupture.