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Papers In Press, published online ahead of print July 1, 2005
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AstraZeneca R&D Mölndal, Discovery Medicine / Molecular Pharmacology, Mölndal SE-431 83
Corresponding Author: pia.davidsson{at}astrazeneca.com
The exchangeable apolipoproteins present in small, dense LDL (sdLDL) and large, buoyant LDL (lbLDL) subclasses were evaluated with a quantitative proteomic approach in patients with the metabolic syndrome and with type 2 diabetes, both with sub clinical atherosclerosis and the B LDL phenotype. The analyses included surface enhanced laser adsorption/ionization, time-of-flight mass spectrometry (SELDI-TOF MS) and subsequent identification by mass spectrometry (MS) or immunoblotting and were carried out in LDL subclasses isolated by ultra centrifugation in D2O gradients with near physiological salt concentrations. The sdLDL of both types of patients were enriched in apoCIII and were depleted of apoCI, apoAI and apoE, when compared with matched healthy controls with the A phenotype. The LDL complexes formed in serum from patients with diabetes with the arterial proteoglycan versican were also enriched in apoCIII. In addition there was a significant correlation between the apoCIII content in sdLDL in patients and the apparent affinity of their LDL for arterial versican. The unique distribution of exchangeable apolipoproteins in the sdLDL of patients studied, especially high apoCIII, coupled with augmented affinity with arterial proteoglycans, may contribute to the strong association of the dyslipidemia of insulin resistance with increased risk for cardiovascular disease.
Revised on June 17, 2005
Accepted on June 18, 2005
Unique distribution of apolipoproteins on small, dense LDL in patients with the metabolic syndrome and type 2 diabetes: a proteomic study
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