caa a22 4500 475772008 CHVBK 20180406123620.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s001250050049 doi (NATIONALLICENCE)springer-10.1007/s001250050049 Glycation impairs high-density lipoprotein function [Elektronische Daten] [C. C. Hedrick, S. R. Thorpe, M.-X. Fu, C. M. Harper, J. Yoo, S.-M. Kim, H. Wong, A. L. Peters] Aims/hypothesis. To examine the effects of incubation of high-density lipoprotein (HDL) under hyperglycaemic conditions on several functions of HDL in vitro.¶Methods. Human HDL (5 mg protein) was incubated for 1 week at 37 °C in the presence or absence of 25 mmol/l glucose. Additional samples of human HDL were incubated in butylated hydroxytoluene to control for oxidation.¶Results. High-density lipoprotein incubated for 1 week in 25 mmol/l glucose had significant increases in the glycation product, fructoselysine and in the advanced glycation end product, N ɛ-(carboxymethyl)-lysine. High-density lipoprotein apolipoprotein AI and AII concentrations were not altered but glycated HDL had a 65 % reduction in paraoxonase enzymatic activity. Glycated HDL did not inhibit monocyte adhesion to human aortic endothelial cells in response to oxidised low-density lipoprotein in vitro (43 ± 4 monocytes bound vs 21 ± 2 monocytes for control HDL, p < 0.0001). Hepatic lipase-mediated non-esterified fatty acid release from HDL lipids was enhanced in glycated HDL compared with control HDL (25 ± 1 vs 16 ± 1 nmol non-esterified fatty acid hydrolysed/min, respectively, p < 0.0001). Direct glycation of purified paraoxonase protein by incubation in 25 mmol/l glucose caused a 40 % reduction in enzymatic activity. This glycated paraoxonase did not inhibit monocyte adhesion to human aortic endothelial cells in vitro (68 ± 3 monocytes vs 49 ± 2 monocytes bound for control paraoxonase, respectively, p < 0.001). We also measured a 40 % reduction in paraoxonase activity in patients with Type II (non-insulin-dependent) diabetes mellitus and documented coronary artery disease compared with non-diabetic subjects, p < 0.0001.¶Conclusions/interpretation. Alterations in function of HDL caused by exposure to hyperglycaemic conditions could contribute to the accelerated atherosclerosis observed in Type II diabetes. [Diabetologia (2000) 43: 312-320] Springer-Verlag Berlin Heidelberg, 2000 Keywords Apolipoprotein AI, apolipoprotein AII, hepatic lipase, high-density lipoprotein, paraoxonase nationallicence Hedrick C. C. Division of Cardiology, University of California School of Medicine, Los Angeles, California, USA, US aut Thorpe S. R. Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, US aut Fu M.-X Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, US aut Harper C. M. Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, US aut Yoo J. Undergraduate Student Research Program, University of California, Los Angeles, California, USA, US aut Kim S.-M Undergraduate Student Research Program, University of California, Los Angeles, California, USA, US aut Wong H. Veterans Administration Wadsworth Medical Center, University of California, Los Angeles, California, USA, US aut Peters A. L. Division of Endocrinology, University of California School of Medicine, Los Angeles, California, USA, US aut https://doi.org/10.1007/s001250050049 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050049 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hedrick C. C. Division of Cardiology, University of California School of Medicine, Los Angeles, California, USA, US aut NATIONALLICENCE 700 1- Thorpe S. R. Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, US aut NATIONALLICENCE 700 1- Fu M.-X Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, US aut NATIONALLICENCE 700 1- Harper C. M. Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, US aut NATIONALLICENCE 700 1- Yoo J. Undergraduate Student Research Program, University of California, Los Angeles, California, USA, US aut NATIONALLICENCE 700 1- Kim S.-M Undergraduate Student Research Program, University of California, Los Angeles, California, USA, US aut NATIONALLICENCE 700 1- Wong H. Veterans Administration Wadsworth Medical Center, University of California, Los Angeles, California, USA, US aut NATIONALLICENCE 700 1- Peters A. L. Division of Endocrinology, University of California School of Medicine, Los Angeles, California, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer