Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictor of Restenosis Following Percutaneous Coronary Intervention

Abstract

Background: Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) increases expression of inflammatory mediators (tumor necrosis factor alpha [TNF-α] and soluble vascular cell adhesion molecule-1 [sVCAM-1]) and induces oxygen radicals that are implicated in atherosclerosis. Balloon-injuryinduced atherosclerosis is associated with increased expression of AGEs and RAGE. The soluble receptor for AGE (sRAGE), which acts as a decoy for RAGE ligands (AGEs), prevents atherosclerosis in this model. Hypothesis: We evaluated: 1) whether post-percutaneous coronary intervention (PCI) restenosis is associated with low pre-PCI serum sRAGE, high serum AGEs, TNF-α, and sVCAM-1, and high AGE/sRAGE ratio; 2) whether pre-PCI and post-PCI levels of these markers are similar in patients with or without restenosis; and 3) whether sRAGE and AGE/sRAGE ratio have predictive value for post-PCI restenosis. Methods: Angiography was performed in 46 patients with non-ST-segment elevation myocardial infarction for assessment of restenosis. Serum sRAGE, AGEs, TNF-α, and sVCAM-1 were measured in these patients and 20 control subjects. Results: Nineteen of the 46 patients developed post-PCI restenosis, which was associated with lower sRAGE and higher TNF-α and sVCAM-1 levels, and higher AGE/sRAGE ratio compared with patients without restenosis. Pre-PCI and post-PCI levels of these biomarkers were similar in both groups, except in patients with restenosis, in whom the post-PCI level of sRAGE was lower and TNF-α was higher than the pre-PCI levels. The sensitivity and negative predictive value of sRAGE were 100%, and were higher than those of AGE/sRAGE ratio in identifying post-PCI restenosis. Conclusions: Both low serum sRAGE levels and high AGE/sRAGE ratio have predictive value for post-PCI restenosis.

Advanced glycation end products (AGEs) in relation to atherosclerotic lipid profiles in middle-aged and elderly diabetic patients

“…These findings were similar to other studies asserting that AGEs may be associated with either control of diabetes or complications of diabetes, and also linked them with diabetes-related complications such as atherosclerosis and restenosis after percutaneous coronary intervention [23-25]…”

Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects

“…Although such an inverse relationship has been described in older apparently healthy adults [49], young and middle-aged subjects did not present any relationship either in our, or in an Italian study [16]. Independent clinical studies suggested that sRAGE or esRAGE could serve as novel biomarkers for estimation of the risk of progression of atherosclerotic disorders [26][27][28]44]. We might speculate that observed Metsy-associated decline in sRAGE might be driven by incipient atherosclerotic changes, and could be later on with manifestation of atherosclerosis reflected by change in CML/sRAGE ratio.…”

“…AGEs and RAGE levels were seldom determined simultaneously. sRAGE -a novel biomarker for estimation of the risk of progression of atherosclerotic disorders [26][27][28] -might be of pathophysiological importance in feedback regulation of the toxic effects of AGE/RAGE-mediated signaling [2,20,27,28]. To elucidate whether alterations in AGE/RAGE axis appear early before manifestation of comorbidities, we investigated whether the increasing number of Metsy risk factors associates with change in circulating AGEs and sRAGE levels in young-tomiddle-aged medication-free non-diabetic subjects.…”

Association of Four Genetic Polymorphisms of AGER and Its Circulating Forms with Coronary Artery Disease: A Meta-Analysis

“…These 27 articles were published between 2004 and 2012, with 4 articles written in Chinese [22], [27], [30], [31] and the others in English. One article was grouped by ethnicity [13] and hypertension [24] respectively, three by CAD subtypes (CAD, MI, CAD with and without restenosis) [14], [17], [25], and five by diabetes mellitus [5], [8], [19], [20], [23]. These independent subgroups were treated separately, and accordingly there were 39 groups in final analyses.…”