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PubMed · 10768092

Glycation impairs high-density lipoprotein function.

C C Hedrick·S R Thorpe·M X Fu·C M Harper·J Yoo·S M Kim·H Wong·A L Peters
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Abstract

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 degrees 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 epsilon-(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.

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AortaAryldialkylphosphataseCell AdhesionDiabetes Mellitus, Type 2Endothelium, VascularEsterasesGlucoseGlycation End Products, AdvancedHumansLipaseLipid MetabolismLipoproteins, HDLLipoproteins, LDLLiverMonocytesOxidation-ReductionSubstrate SpecificityJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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C C Hedrick, S R Thorpe, M X Fu, C M Harper, J Yoo, S M Kim, H Wong, A L Peters. 2000. Glycation impairs high-density lipoprotein function.. https://doi.org/10.1007/s001250050049

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