Soluble lectin-like oxidized low density lipoprotein receptor-1 in type 2 diabetes mellitus

Kathryn C.B Tan,Sammy W.M Shiu,Ying Wong,Lin Leng,Richard Bucala

doi:10.1194/jlr.m700551-jlr200

Abstract

The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms (sLOX-1). We have determined serums LOX-1 in type 2 diabetes and evaluated the effect of glucose and advanced glycation end products (AGEs) on sLOX-1 in vitro and in vivo. Endothelial cells were incubated with glucose or AGEs, and sLOX-1 in cell medium was measured. Serum sLOX-1 was measured in 219 diabetic patients and 187 controls by ELISA. The effect of lowering glucose and AGEs on sLOX-1 was determined in 38 poorly controlled diabetic patients after improvement in glycemic control. Incubation of endothelial cells with AGE-BSA led to a dose-dependent increase in sLOX-1, whereas the effect of glucose on sLOX-1 was less marked. Serum sLOX-1 was 9% higher in diabetic patients compared with controls (P<0.01). In the poorly controlled patients, serum sLOX-1 decreased by 12.5% after improvement in glycemic control (P<0.05). The magnitude of reduction in sLOX-1 correlated with the improvement in hemoglobin A1c and AGEs but not with the reduction in oxidized LDL. sLOX-1 level is increased in type 2 diabetes. Both glucose and AGEs are important determinants of LOX-1 expression, and lowering glucose and AGEs leads to a reduction in sLOX-1.

Highlights

The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms
The effect of advanced glycation end products (AGEs)-BSA or glucose on LOX-1 expression in endothelial cells was investigated in vitro, and analysis of cell lysates demonstrated that stimulation of cells with AGE-BSA or glucose increased LOX-1 expression (Fig. 1A, B)
The effect of glucose on sLOX-1 was less marked, and we only observed a significant increase in sLOX-1 concentration at high glucose concentration (Fig. 2B)

Summary

Introduction

The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms (sLOX-1). The lectin-like oxidized low density lipoprotein receptor (LOX-1), a class E scavenger receptor, is a newly identified oxidized LDL (oxLDL) receptor mainly expressed by endothelial cells [1]. Since LOX-1 expression can be upregulated by glucose and by AGEs in vitro [12,13,14,15,16], we have determined whether this was associated with an increase in the release of the soluble forms of the receptor in conditioned medium. We further investigated whether serum sLOX-1 concentration was increased in patients with type 2 diabetes mellitus and evaluated the impact of lowering glucose and AGEs by improving glycemic control on serum sLOX-1 concentration

Methods

Results

Conclusion