Impact of serum amyloid A on cellular cholesterol efflux to serum in type 2 diabetes mellitus

Atherosclerosis. 2013 Dec;231(2):405-10. doi: 10.1016/j.atherosclerosis.2013.10.008. Epub 2013 Oct 18.

Abstract

Objective: Serum amyloid A (SAA) is an acute phase response protein and has apolipoprotein properties. Since type 2 diabetes is associated with chronic subclinical inflammation, the objective of this study is to investigate the changes in SAA level in type 2 diabetic patients and to evaluate the relationship between SAA and the capacity of serum to induce cellular cholesterol efflux via the two known cholesterol transporters, scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G1 (ABCG1).

Methods: 264 patients with type 2 diabetes mellitus (42% with normoalbuminuria, 30% microalbuminuria, and 28% proteinuria) and 275 non-diabetic controls were recruited. SAA was measured by ELISA. SR-BI and ABCG1-mediated cholesterol efflux to serum were determined by measuring the transfer of [(3)H]cholesterol from Fu5AH rat hepatoma cells expressing SR-BI and from human ABCG1-transfected CHO-K1 cells to the medium containing the tested serum respectively.

Results: SAA was significantly increased in diabetic patients with incipient or overt nephropathy. Both SR-BI and ABCG1-mediated cholesterol efflux to serum were significantly impaired in all three groups of diabetic patients (p < 0.01). SAA inversely correlated with SR-BI-mediated cholesterol efflux (r = -0.36, p < 0.01) but did not correlate with ABCG1-mediated cholesterol efflux. Stepwise linear regression analysis showed that HDL, the presence or absence of diabetes, and log(SAA) were significant independent determinants of SR-BI-mediated cholesterol efflux to serum.

Conclusion: SAA was increased in type 2 diabetic patients with incipient or overt nephropathy, and SAA was associated with impairment of SR-BI-mediated cholesterol efflux to serum.

Keywords: ATP-binding cassette transporter G1; Cellular cholesterol efflux; High density lipoprotein; Reverse cholesterol transport; Scavenger receptor class B type I; Serum amyloid A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / blood*
  • Adult
  • Aged
  • Animals
  • Apolipoproteins / blood*
  • CHO Cells
  • Cell Line, Tumor
  • Cholesterol / blood*
  • Cholesterol, HDL / blood
  • Cricetinae
  • Cricetulus
  • Diabetes Complications / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Rats
  • Scavenger Receptors, Class B / blood*
  • Serum Amyloid A Protein / metabolism*

Substances

  • ABCG1 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins
  • Cholesterol, HDL
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Serum Amyloid A Protein
  • Cholesterol