Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

Olga V Savinova,Gregory C Shearer,Linhong Jing,William S Harris,Kristi Fillaus,Patricia Aspichueta

doi:10.1371/journal.pone.0104833

Olga V Savinova, Gregory C Shearer + Show 4 more

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https://doi.org/10.1371/journal.pone.0104833

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Abstract

ObjectiveThe purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.MethodsVery low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.ResultsMetabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma - apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL - apoB, apoC3, and apoE were increased; (3) LDL - apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001).ConclusionsPatients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

Highlights

The prevalence of metabolic syndrome (MetSyn) in the US and worldwide remains high [1,2,3,4,5] and is associated with the increased cardiovascular disease (CVD) risk [6,7]
The diagnosis of MetSyn is based on the presence of any three or more components from the list of central obesity; reduced high density lipoprotein cholesterol (HDL-C); elevated plasma triglycerides (TG) or glucose; or high blood pressure [8]
Differences in body mass index (BMI), triglyceride and high density lipoproteins (HDL)-cholesterol levels were a reflection of the different inclusion/exclusion criteria for these two groups of subjects

Summary

Introduction

The prevalence of metabolic syndrome (MetSyn) in the US and worldwide remains high [1,2,3,4,5] and is associated with the increased cardiovascular disease (CVD) risk [6,7]. The diagnosis of MetSyn is based on the presence of any three or more components from the list of central obesity; reduced high density lipoprotein cholesterol (HDL-C); elevated plasma triglycerides (TG) or glucose; or high blood pressure [8]. The levels of apoB (found in very low, low and intermediate density lipoproteins; VLDL, LDL, and IDL, respectively) and apoA1 (in HDL). A perturbation in apo levels would not be surprising in MetSyn given the fact that apoB is closely associated with abdominal obesity and other features of MetSyn [14]. Some evidence of apo composition of lipoprotein classes in MetSyn is available from the proteomic studies: HDL (HDL3 subclass) isolated from dyslipidemic subjects (with new diagnosis of coronary artery disease) were reported to be enriched in apoE [18]; whereas LDL (small dense LDL subclass) from a different cohort of subjects with MetSyn were enriched in apoC3 and depleted of apoC1, apoA1, and apoE compared with matched healthy controls [19]

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