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Int. J. Mol. Sci. 2019, 20(3), 732; https://doi.org/10.3390/ijms20030732

Antibodies Against the C-Terminus of ApoA-1 Are Inversely Associated with Cholesterol Efflux Capacity and HDL Metabolism in Subjects with and without Type 2 Diabetes Mellitus

1
Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
2
Division of Laboratory Medicine, Department of Diagnostics, Hộpitaux Universitaires de Geneve, 1211 Geneva, Switzerland
3
Department of Internal Medicine Specialities, Medical Faculty, Hộpitaux Universitaires de Geneve, 1211 Geneva, Switzerland
*
Author to whom correspondence should be addressed.
Received: 22 January 2019 / Revised: 6 February 2019 / Accepted: 6 February 2019 / Published: 9 February 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Background: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). Methods: In 75 T2D subjects and 75 nondiabetic subjects, Ac-terAA1 and AAA1 plasma levels were measured by enzyme-linked immunosorbent assay. CEC was measured as [3H]-cholesterol efflux from human cultured fibroblasts to diluted individual subject plasma. Plasma EST and CET were assayed by isotope methods. Results: Ac-terAA1 and AAA1 levels and were similar between T2D and control subjects. Univariate regression analysis (n = 150) demonstrated that Ac-terAA1 levels were inversely correlated with CEC, EST, CET, total cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B, (p < 0.05 to p < 0.01), but not with glucose and HbA1c. In separate multivariable linear regression models, CEC, EST and CET were inversely associated with Ac-terAA1 levels independently of age, sex, T2D and drug use (β = −0.186, p = 0.026; β = −0.261, p < 0.001; and β = −0.321, p < 0.001; respectively). These associations were lost after additional adjustment for non-HDL cholesterol and triglycerides. No associations were observed for AAA1. Conclusions: CEC, plasma EST and CET are inversely associated with Ac-terAA1 autoantibodies, conceivably attributable to an inverse relationship of these autoantibodies with apolipoprotein B-containing lipoproteins. View Full-Text
Keywords: anti-apoA-1 autoantibodies; cholesterol efflux capacity; cholesterol esterification; cholesteryl ester transfer; high-density lipoproteins; Type 2 diabetes mellitus anti-apoA-1 autoantibodies; cholesterol efflux capacity; cholesterol esterification; cholesteryl ester transfer; high-density lipoproteins; Type 2 diabetes mellitus
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Dullaart, R.P.F.; Pagano, S.; Perton, F.G.; Vuilleumier, N. Antibodies Against the C-Terminus of ApoA-1 Are Inversely Associated with Cholesterol Efflux Capacity and HDL Metabolism in Subjects with and without Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2019, 20, 732.

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