HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: clinchem.2007.099747v1 54/6/1038    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Lambert, G. Articles by Barter, P. J. Search for Related Content PubMed PubMed Citation Articles by Lambert, G. Articles by Barter, P. J. Related Collections Lipids, Lipoproteins, and Cardiovascular Risk Factors

Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment

¹ The Heart Research Institute, Sydney, Australia; ² Université de Nantes, INSERM U539, Nantes, France; ³ GlaxoSmithKline, CVU CEDD, Les Ulis, France; ⁴ the Royal Prince Alfred Hospital, Sydney, Australia; ⁵ The University of Sydney, Sydney, Australia.

^aAddress correspondence to this author at: the Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown NSW 2050, Australia. Fax +61 2 9565 5584; e-mail lambertg{at}hri.org.au

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.

Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment.

Results: We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048).

Conclusions: We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol–lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.

The following articles in journals at HighWire Press have cited this article:

				D. L. Rainwater, L. A. Cox, J. Rogers, J. L. VandeBerg, and M. C. Mahaney Localization of multiple pleiotropic genes for lipoprotein metabolism in baboons J. Lipid Res., July 1, 2009; 50(7): 1420 - 1428. [Abstract] [Full Text] [PDF]

				M. C. McNutt, H. J. Kwon, C. Chen, J. R. Chen, J. D. Horton, and T. A. Lagace Antagonism of Secreted PCSK9 Increases Low Density Lipoprotein Receptor Expression in HepG2 Cells J. Biol. Chem., April 17, 2009; 284(16): 10561 - 10570. [Abstract] [Full Text] [PDF]

				J. D. Horton, J. C. Cohen, and H. H. Hobbs PCSK9: a convertase that coordinates LDL catabolism J. Lipid Res., April 1, 2009; 50(Supplement): S172 - S177. [Abstract] [Full Text] [PDF]