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Originally published In Press as doi:10.1194/jlr.M500161-JLR200 on July 1, 2005

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Journal of Lipid Research, Vol. 46, 1999-2006, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

A proteomic study of the apolipoproteins in LDL subclasses in patients with the metabolic syndrome and type 2 diabetes

Pia Davidsson1,*, Johannes Hulthe*, Björn Fagerberg{dagger}, Britt-Marie Olsson*, Carina Hallberg*, Björn Dahllöf* and Germán Camejo*

* AstraZeneca R&D Mölndal, Mölndal, Sweden
{dagger} Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden

Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.M500161-JLR200

1 To whom correspondence should be addressed. e-mail: pia.davidsson{at}astrazeneca.com

The exchangeable apolipoproteins present in small, dense LDL (sdLDL) and large, buoyant LDL subclasses were evaluated with a quantitative proteomic approach in patients with the metabolic syndrome and with type 2 diabetes, both with subclinical atherosclerosis and the B LDL phenotype. The analyses included surface-enhanced laser adsorption/ionization, time-of-flight mass spectrometry, and subsequent identification by mass spectrometry or immunoblotting and were carried out in LDL subclasses isolated by ultracentrifugation in deuterium oxide gradients with near physiological salt concentrations. The sdLDLs of both types of patients were enriched in apolipoprotein C-III (apoC-III) and were depleted of apoC-I, apoA-I, and apoE compared with matched healthy controls with the A phenotype. The LDL complexes formed in serum from patients with diabetes with the arterial proteoglycan (PG) versican were also enriched in apoC-III. In addition, there was a significant correlation between the apoC-III content in sdLDL in patients and the apparent affinity of their LDLs for arterial versican.

The unique distribution of exchangeable apolipoproteins in the sdLDLs of the patients studied, especially high apoC-III, coupled with the augmented affinity with arterial PGs, may contribute to the strong association of the dyslipidemia of insulin resistance with increased risk for cardiovascular disease.

Supplementary key words mass spectrometry • apolipoprotein C-III • apolipoprotein C-I • apolipoprotein E • apolipoprotein A-I • low density lipoproteins • B phenotype


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