ELEVATED AGE-MODIFIED APO-B IN SERA OF EUGLYCEMIC, NORMOLIPIDEMIC PATIENTS WITH ATHEROSCLEROSIS - RELATIONSHIP TO TISSUE AGES

Background: Advanced glycation endproducts (AGEs) are implicated in th e pathogenesis of atherosclerotic vascular disease of diabetic and non diabetic etiology. Recent research suggests that advanced glycation of ApoB contributes to the development of hyperlipidemia. AGE-specific r eceptors, expressed on vascular endothelium and mononuclear cells, may be involved in both the clearance of, and the inflammatory responses to AGEs. The aim of this study was to examine whether there is a relat ionship between serum AGE-ApoB and AGEs in arterial tissue of older no rmolipidemic nondiabetic patients with occlusive atherosclerotic disea se, compared with age-matched and younger asymptomatic persons. Materi als and Methods: Serum AGE-ApoB was measured by ELISA in 21 cardiac by pass patients. Furthermore, an AGE-specific monoclonal antibody, and p olyclonal antibodies against anti-AGE-receptor (anti-AGE-R) 1 and 2 we re used to explore the localization and distribution of AGEs and AGE-R immunoreactivity (1R) in arterial segments excised from these patient s. Results: Serum AGE-ApoB levels were significantly elevated in the a symptomatic, older population, compared with those in young healthy pe rsons (259 +/- 24 versus 180 +/- 21 AGE U/mg of ApoB, p < 0.01). Highe r AGE-ApoB levels were observed in those patients with atherosclerosis (329 +/- 23 versus 259 +/- 24 AGE U/mg ApoB, p < 0.05). Comparisons o f tissue AGE-collagen with serum AGE-ApoB levels showed a significant correlation (r = 0.707, p < 0.01). In early lesions, AGE-IR occurred m ostly extracellularly. In fatty streaks and dense, cellular atheromato us lesions, AGE-IR was visible within lipid-containing smooth muscle c ells and macrophages, while in late-stage, acellular plaques, AGE-IR o ccurred mostly extracellularly. AGE-R1 and -R2 were observed on vascul ar endothelial and smooth-muscle cells and on infiltrating mononuclear cells in the early stage lesions, whereas in dense, late-stage plaque s, they colocalized mostly with lipid-laden macrophages. On tissue sec tions, scoring of AGE-immunofluorescence correlated with tissue AGE an d plasma AGE-ApoB. Conclusions: (1) The correlation between arterial t issue AGEs and circulating AGE-ApoB suggests a causal link between AGE modification of lipoproteins and atherosclerosis. AGE-specific recept ors may contribute to this process. (2) Serum AGE-ApoB may serve to pr edict atherosclerosis in asymptomatic patients.