Non-enzymatic glycation of serum apolipoproteins is a main feature of diabetes mellitus under hyperglycemia Advanced glycation end products are implicated in the development of aging and metabolic syndrome, including premature atherosclerosis in diabetic subjects ApoA-I is the principal protein constituent of HDL. In this study. glycated human apoA-I (gA-I) by fructation was characterized on functional and Structural correlations in lipid-free and lipid-bound states The gA-I showed more spontaneous multimetric band formation up to pentamer and exhibited slower elution profile with more degraded fragments from fast protein liquid chromatography The gA-I showed modified secondary structure from fluorescence and circular dichroism analysis Reconstituted high-density lipoprotein (rHDL) containing the gA-I had less content of phospholipid with a much smaller particle size than those of rHDL-containing nA-I (nA-I-rHDL). The rHDL containing gA-I (gA-I-rHDL) consisted of less molecular number of apoA-I than nA-I-rHDL with decreased alpha-helical content. Treatment of the gA-I-rHDL induced more atherogenic process in macrophage cell and premature senescence in human dermal fibroblast cell Conclusively, fructose-mediated apoA-I glycation resulted in severe loss of several beneficial functions of apoA-I and HDL regarding anti-senescence and anti-atherosclerosis activities due to a lack of anti-oxidant activity with increased susceptibility of protein degradation and structural modification (C) 2010 Elsevier Inc All rights reserved