Submitted on November 27, 2007
Revised on April 4, 2008
Accepted on April 11, 2008
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, and Richard Bucala
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
Corresponding Author: kcbtan{at}hkucc.hku.hk
Objective: The lectin-like oxidized LDL receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms (sLOX-1). We have determined serum sLOX-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. Methods: 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. Results: 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 to 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 HbA1c and AGEs but not with the reduction in oxidized LDL. Conclusion: 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.
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