Article: Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes
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- Publisher Website: 10.1016/j.atherosclerosis.2009.08.031
- Scopus: eid_2-s2.0-77049119450
- PMID: 19733353
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| Title | Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Tam, HL1 Shiu, SWM1 Wong, Y1 Chow, WS1 Betteridge, DJ2 Tan, KCB1 | ||||||
| Keywords | Advanced glycation end-products Atorvastatin Soluble receptor for advanced glycation end-products Type 2 diabetes mellitus | ||||||
| Issue Date | 2010 | ||||||
| Publisher | Elsevier 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?] DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031 | ||||||
| Abstract | 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 240.5 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. | ||||||
| ISSN | 0021-9150 2011 Impact Factor: 3.794 2011 SCImago Journal Rankings: 0.372 | ||||||
| DOI | http://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031 | ||||||
| ISI Accession Number ID | WOS:000275101500028
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 | References in Scopus | ||||||
| Grants | Soluble receptor for advanced glycation end products and diabetic complications |
| dc.contributor.author | Tam, HL | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Shiu, SWM | ||||||
| dc.contributor.author | Wong, Y | ||||||
| dc.contributor.author | Chow, WS | ||||||
| dc.contributor.author | Betteridge, DJ | ||||||
| dc.contributor.author | Tan, KCB | ||||||
| dc.date.accessioned | 2010-10-31T11:09:56Z | ||||||
| dc.date.available | 2010-10-31T11:09:56Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | 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 240.5 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.grant | Soluble receptor for advanced glycation end products and diabetic complications | ||||||
| dc.description.grantcode | 99048 | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Atherosclerosis, 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.citeulike | 5627978 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.atherosclerosis.2009.08.031 | ||||||
| dc.identifier.epage | 177 | ||||||
| dc.identifier.hkuros | 174655 | ||||||
| dc.identifier.isi | WOS:000275101500028
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.issn | 0021-9150 2011 Impact Factor: 3.794 2011 SCImago Journal Rankings: 0.372 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 19733353 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77049119450 | ||||||
| dc.identifier.spage | 173 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/125074 | ||||||
| dc.identifier.volume | 209 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/atherosclerosis | ||||||
| dc.publisher.place | Ireland | ||||||
| dc.relation.ispartof | Atherosclerosis | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Diabetes Mellitus, Type 2 - blood - drug therapy | ||||||
| dc.subject.mesh | Heptanoic Acids - therapeutic use | ||||||
| dc.subject.mesh | Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use | ||||||
| dc.subject.mesh | Pyrroles - therapeutic use | ||||||
| dc.subject.mesh | Receptors, Immunologic - blood | ||||||
| dc.subject | Advanced glycation end-products | ||||||
| dc.subject | Atorvastatin | ||||||
| dc.subject | Soluble receptor for advanced glycation end-products | ||||||
| dc.subject | Type 2 diabetes mellitus | ||||||
| dc.title | Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- UCL Medical School