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Article: Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes
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TitleEffects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes
 
AuthorsTam, HL1
Shiu, SWM1
Wong, Y1
Chow, WS1
Betteridge, DJ2
Tan, KCB1
 
KeywordsAdvanced glycation end-products
Atorvastatin
Soluble receptor for advanced glycation end-products
Type 2 diabetes mellitus
 
Issue Date2010
 
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/atherosclerosis
 
CitationAtherosclerosis, 2010, v. 209 n. 1, p. 173-177 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031
 
AbstractObjective: 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 240.5 pg/ml (interquartile range 186.5-377.3) vs 194.8 pg/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. © 2009 Elsevier Ireland Ltd. All rights reserved.
 
ISSN0021-9150
2013 Impact Factor: 3.971
2013 SCImago Journal Rankings: 1.728
 
DOIhttp://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031
 
ISI Accession Number IDWOS:000275101500028
Funding AgencyGrant Number
Hong Kong Research Grants Council Research FundHKU 775708M
Committee on Research and Conference Grants of the University of Hong Kong
Funding Information:

This study is supported by funding from the Hong Kong Research Grants Council Research Fund (HKU 775708M) and the Committee on Research and Conference Grants of the University of Hong Kong.

 
ReferencesReferences in Scopus
 
GrantsSoluble receptor for advanced glycation end products and diabetic complications
 
DC FieldValue
dc.contributor.authorTam, HL
 
dc.contributor.authorShiu, SWM
 
dc.contributor.authorWong, Y
 
dc.contributor.authorChow, WS
 
dc.contributor.authorBetteridge, DJ
 
dc.contributor.authorTan, KCB
 
dc.date.accessioned2010-10-31T11:09:56Z
 
dc.date.available2010-10-31T11:09:56Z
 
dc.date.issued2010
 
dc.description.abstractObjective: 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 240.5 pg/ml (interquartile range 186.5-377.3) vs 194.8 pg/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. © 2009 Elsevier Ireland Ltd. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationAtherosclerosis, 2010, v. 209 n. 1, p. 173-177 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031
 
dc.identifier.citeulike5627978
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031
 
dc.identifier.eissn1879-1484
 
dc.identifier.epage177
 
dc.identifier.hkuros174655
 
dc.identifier.isiWOS:000275101500028
Funding AgencyGrant Number
Hong Kong Research Grants Council Research FundHKU 775708M
Committee on Research and Conference Grants of the University of Hong Kong
Funding Information:

This study is supported by funding from the Hong Kong Research Grants Council Research Fund (HKU 775708M) and the Committee on Research and Conference Grants of the University of Hong Kong.

 
dc.identifier.issn0021-9150
2013 Impact Factor: 3.971
2013 SCImago Journal Rankings: 1.728
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmid19733353
 
dc.identifier.scopuseid_2-s2.0-77049119450
 
dc.identifier.spage173
 
dc.identifier.urihttp://hdl.handle.net/10722/125074
 
dc.identifier.volume209
 
dc.languageeng
 
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/atherosclerosis
 
dc.publisher.placeIreland
 
dc.relation.ispartofAtherosclerosis
 
dc.relation.projectSoluble receptor for advanced glycation end products and diabetic complications
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshDiabetes Mellitus, Type 2 - blood - drug therapy
 
dc.subject.meshHeptanoic Acids - therapeutic use
 
dc.subject.meshHydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
 
dc.subject.meshPyrroles - therapeutic use
 
dc.subject.meshReceptors, Immunologic - blood
 
dc.subjectAdvanced glycation end-products
 
dc.subjectAtorvastatin
 
dc.subjectSoluble receptor for advanced glycation end-products
 
dc.subjectType 2 diabetes mellitus
 
dc.titleEffects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes
 
dc.typeArticle
 
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<contributor.author>Betteridge, DJ</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. UCL Medical School