Glycation impairs high-density lipoprotein function (original) (raw)

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 °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]

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Authors and Affiliations

  1. Division of Cardiology, University of California School of Medicine, Los Angeles, California, USA, , , , , , US
    C. C. Hedrick
  2. Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA, , , , , , US
    S. R. Thorpe, M.-X. Fu & C. M. Harper
  3. Undergraduate Student Research Program, University of California, Los Angeles, California, USA, , , , , , US
    J. Yoo & S.-M. Kim
  4. Veterans Administration Wadsworth Medical Center, University of California, Los Angeles, California, USA, , , , , , US
    H. Wong
  5. Division of Endocrinology, University of California School of Medicine, Los Angeles, California, USA, , , , , , US
    A. L. Peters

Authors

  1. C. C. Hedrick
  2. S. R. Thorpe
  3. M.-X. Fu
  4. C. M. Harper
  5. J. Yoo
  6. S.-M. Kim
  7. H. Wong
  8. A. L. Peters

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Received: 16 June 1999 and in final revised form: 18 October 1999

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Hedrick, C., Thorpe, S., Fu, MX. et al. Glycation impairs high-density lipoprotein function.Diabetologia 43, 312–320 (2000). https://doi.org/10.1007/s001250050049

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