Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes.
OBJECTIVE
The receptor for advanced glycation end-products (RAGE) plays an important role in the pathogenesis of diabetic complications and atherosclerosis. Interfering with the activation of RAGE by using a soluble form of the receptor (sRAGE) ameliorates the vascular complications of diabetes in animal models. We have investigated whether statin can influence the expression of sRAGE and esRAGE (a splice variant of sRAGE) in vitro and in vivo.


METHODS
THP-1 cells were incubated with atorvastatin in vitro and sRAGE and esRAGE in the medium was measured by Western immunoblot. Serum levels of sRAGE and esRAGE were measured by ELISA in archived serum samples from a previous randomized double-blind placebo-controlled clinical trial that explored the cardiovascular effects of atorvastatin in hypercholesterolemic Chinese type 2 diabetic patients.


RESULTS
sRAGE and esRAGE were induced by atorvastatin in a time- and dose-dependent manner in THP-1 cells. In the diabetic patients, there was a significant increase in serum sRAGE (p<0.05) and esRAGE (p<0.01) in the atorvastatin group at 6-month, but no change in placebo group. Serum esRAGE was higher in atorvastatin group than placebo group [median 240.5pg/ml (interquartile range 186.5-377.3) vs 194.8pg/ml (124.1-347.9) respectively, p<0.01] at 6-month, whereas the differences in sRAGE did not reach statistical significance (p=0.051). There was a correlation between the increase of serum esRAGE and reduction of serum LDL (r=-0.36, p=0.001).


CONCLUSIONS
Statins are known to have pleiotropic effects and we have shown that atorvastatin can increase circulating esRAGE levels in type 2 diabetic patients.
Tam
H L
HL
Department of Medicine, University of Hong Kong, Hong Kong.
Shiu
S W M
SW
Wong
Y
Y
Chow
W S
WS
Betteridge
D J
DJ
Tan
K C B
KC
D044466:Asian People; D000069059:Atorvastatin; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000069059:Atorvastatin