Cellular cholesterol efflux to serum is impaired in diabetic nephropathy

Diabetes Metab Res Rev. Nov-Dec 2008;24(8):617-23. doi: 10.1002/dmrr.895.

Abstract

Background: Cholesterol efflux from cells is an early step of reverse cholesterol transport (RCT) and the capacity of serum to induce cellular cholesterol efflux has recently been shown to be an independent predictor of coronary artery atherosclerosis. Our aim is to evaluate the capacity of serum to induce ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) mediated cholesterol efflux in type 2 diabetic patients with nephropathy.

Methods: Diabetic patients were recruited according to their urinary albumin excretion rate (normoalbuminuria, microalbuminuria and proteinuria) with 20 subjects in each group and compared with 20 age-matched controls. The ability of the serum to induce cholesterol efflux was measured using a cell culture system.

Results: Serum capacity to induce ABCA1-mediated cholesterol efflux was decreased in patients with microalbuminuria or proteinuria (p < 0.05) whereas SR-BI-mediated cholesterol efflux was impaired in all three groups of diabetic patients (p < 0.05). Plasma high-density lipoprotein (HDL) cholesterol and apoAI were reduced in all groups of diabetic patients, but pre-beta-HDL was only significantly decreased in those with microalbuminuria or proteinuria. Serum advanced glycation end products (AGEs) were significantly increased in diabetic patients with microalbuminuria or proteinuria. Serum AGEs and pre-beta-HDL were the significant independent determinants of ABCA1-mediated cholesterol efflux, whereas plasma HDL and log (creatinine) were the significant determinants of SR-BI-mediated cholesterol efflux.

Conclusion: The capacity of serum to induce ABCA1- and SR-BI-mediated cholesterol efflux was impaired in diabetic patients with incipient or overt nephropathy. These abnormalities may contribute to the accelerated development of atherosclerotic vascular disease in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / blood
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Albuminuria / blood
  • Albuminuria / metabolism
  • Analysis of Variance
  • Biological Transport
  • Blood Glucose / analysis
  • Cholesterol / blood*
  • Cholesterol / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Nephropathies / blood*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Lipids / blood
  • Male
  • Middle Aged
  • Proteinuria / blood
  • Proteinuria / metabolism
  • RNA, Messenger / genetics
  • Scavenger Receptors, Class B / blood
  • Scavenger Receptors, Class B / metabolism

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Blood Glucose
  • Glycated Hemoglobin A
  • Lipids
  • RNA, Messenger
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Cholesterol