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Article: Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes

TitleEffects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes
Authors
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
Citation
Atherosclerosis, 2010, v. 209 n. 1, p. 173-177 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/125074
ISSN
2014 Impact Factor: 3.994
2014 SCImago Journal Rankings: 1.529
ISI Accession Number ID
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.

References
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DC FieldValueLanguage
dc.contributor.authorTam, HLen_HK
dc.contributor.authorShiu, SWMen_HK
dc.contributor.authorWong, Yen_HK
dc.contributor.authorChow, WSen_HK
dc.contributor.authorBetteridge, DJen_HK
dc.contributor.authorTan, KCBen_HK
dc.date.accessioned2010-10-31T11:09:56Z-
dc.date.available2010-10-31T11:09:56Z-
dc.date.issued2010en_HK
dc.identifier.citationAtherosclerosis, 2010, v. 209 n. 1, p. 173-177en_HK
dc.identifier.issn0021-9150en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125074-
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.en_HK
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/atherosclerosisen_HK
dc.relation.ispartofAtherosclerosisen_HK
dc.subjectAdvanced glycation end-productsen_HK
dc.subjectAtorvastatinen_HK
dc.subjectSoluble receptor for advanced glycation end-productsen_HK
dc.subjectType 2 diabetes mellitusen_HK
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.titleEffects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9150&volume=209&issue=1&spage=173&epage=177&date=2010&atitle=Effects+of+atorvastatin+on+serum+soluble+receptors+for+advanced+glycation+end-products+in+type+2+diabetesen_HK
dc.identifier.emailTan, KCB:kcbtan@hku.hken_HK
dc.identifier.authorityTan, KCB=rp00402en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.atherosclerosis.2009.08.031en_HK
dc.identifier.pmid19733353en_HK
dc.identifier.scopuseid_2-s2.0-77049119450en_HK
dc.identifier.hkuros174655en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77049119450&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume209en_HK
dc.identifier.issue1en_HK
dc.identifier.spage173en_HK
dc.identifier.epage177en_HK
dc.identifier.eissn1879-1484-
dc.identifier.isiWOS:000275101500028-
dc.publisher.placeIrelanden_HK
dc.relation.projectSoluble receptor for advanced glycation end products and diabetic complications-
dc.identifier.scopusauthoridTam, HL=36129024100en_HK
dc.identifier.scopusauthoridShiu, SWM=7005550652en_HK
dc.identifier.scopusauthoridWong, Y=24073787400en_HK
dc.identifier.scopusauthoridChow, WS=7402281153en_HK
dc.identifier.scopusauthoridBetteridge, DJ=34973752700en_HK
dc.identifier.scopusauthoridTan, KCB=8082703100en_HK
dc.identifier.citeulike5627978-

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