Association between serum amyloid A and scavenger receptor class B type 1-mediated cholesterol efflux to serum in type 2 diabetes

Abstract

Serum amyloid A (SAA) is an acute phase response protein and has apolipoprotein properties. Recent evidence from animal studies has shown that SAA impairs reverse cholesterol transport during the acute phase response in vivo. Since type 2 diabetes is associated with chronic subclinical inflammation, the objective 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 adenosine triphosphate binding cassette transporter G1 (ABCG1). 264 diabetic patients not on lipid lowering agents and 275 non-diabetic controls were recruited. Diabetic patients were subdivided into those with normoalbuminuria (NA, n=110), microalbuminuria (MA, n=79) and proteinuria (P, n=75). SAA was measured by ELISA. SR-BI-mediated and ABCG1-mediated cholesterol efflux to serum was determined by measuring the transfer of [3H]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. SAA was increased in MA and P (p<0.01) compared to controls. Both SR-BI-mediated and ABCG1-mediated cholesterol efflux to serum was significantly impaired in all 3 groups of diabetic patients (p<0.01) with the proteinuric group having the largest magnitude of reduction. These changes remained significant even after adjusting for plasma HDL-C level. SAA inversely correlated with SR-BI-mediated cholesterol efflux (r=-0.36, p<0.01) but not with ABCG1-mediated cholesterol efflux. On linear regression analysis, plasma HDL-C, SAA and eGFR were independent determinants of SR-BI-mediated cholesterol efflux. SAA was increased in type 2 diabetic patients with incipient or overt nephropathy and associated with impairment of SR-BI-mediated cholesterol efflux to serum.