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

Abstract

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. -Davidsson, P., J. Hulthe, B. Fagerberg, B-M. Olsson, C. Hallberg, B. Dahllöf, and G. Camejo. A proteomic study of the apolipoproteins in LDL subclasses in patients with the metabolic syndrome and type 2 diabetes.

A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

“…Previous studies have already proved the increased atherogenic properties of small dense LDL particles of DM patients ( 54 ). This study highlights the potential relevance of ApoA-I truncated forms in relation to this increased cardiovascular risk of DM patients.…”

Proteomic analysis of electronegative low-density lipoprotein

“…Albeit in a lower concentration, other proteins that were always detected in one or both LDL fractions were apoC-I, apoD, apoJ, apoF, SAA4, albumin, apo(a), and platelet basic protein. With the exception of the platelet basic protein, the presence of all these proteins has been previously described in LDL (4)(5)(6)(7)(8)(9).…”

“…Some of them, such as apoC-IV, apoA-IV, PAF-AH, calgranulin, and SAA2, have been previously reported to be associated with lipoproteins (3)(4)(5)(6)(7)(8)(9)23 ). Others are known to be involved in innate immunity, infl ammation, and coagulation.…”

Human body fluid proteome analysis

“…The small, dense LDLs of diabetes patients were found enriched in apo C-III and depleted of apo C-I, apo A-I, and apo E compared with matched healthy controls [261]. Serum proteomic pattern analysis could be used for evaluation of periodic hemodialysis treatment [262] and for assessment of the remission from active Wegener's granulomatosis [263].…”