A Shift in ApoM/S1P between HDL-Particles in Women with Type 1 Diabetes Mellitus Is Associated with Impaired Anti-Inflammatory Effects of the ApoM/S1P Complex

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@article{8c2aee10537e4512b77df63d3e34a5da,
title = "A Shift in ApoM/S1P between HDL-Particles in Women with Type 1 Diabetes Mellitus Is Associated with Impaired Anti-Inflammatory Effects of the ApoM/S1P Complex",
abstract = "Objective-Type 1 diabetes mellitus (T1D) patients have an increased risk of cardiovascular disease despite high levels of high-density lipoproteins (HDL). Apolipoprotein M (apoM) and its ligand sphingosine 1-phospate (S1P) exert many of the anti-inflammatory effects of HDL. We investigated whether apoM and S1P are altered in T1D and whether apoM and S1P are important for HDL functionality in T1D. Approach and Results-ApoM and S1P were quantified in plasma from 42 healthy controls and 89 T1D patients. HDL was isolated from plasma and separated into dense, medium-dense, and light HDL by ultracentrifugation. Primary human aortic endothelial cells were challenged with tumor necrosis factor-α in the presence or absence of isolated HDL. Proinflammatory adhesion molecules E-selectin and vascular cellular adhesion molecule-1 were quantified by flow cytometry. Activation of the S1P1-receptor was evaluated by analyzing downstream signaling targets and receptor internalization. There were no differences in plasma levels of apoM and S1P between controls and T1D patients, but the apoM/S1P complexes were shifted from dense to light HDL particles in T1D. ApoM/S1P in light HDL particles from women were less efficient in inhibiting expression of vascular cellular adhesion molecule-1 than apoM/S1P in denser particles. The light HDL particles were unable to activate Akt, whereas all HDL subfractions were equally efficient in activating Erk and receptor internalization. Conclusions-ApoM/S1P in light HDL particles were inefficient in inhibiting tumor necrosis factor-α-induced vascular cellular adhesion molecule-1 expression in contrast to apoM/S1P in denser HDL particles. T1D patients have a higher proportion of light particles and hence more dysfunctional HDL, which could contribute to the increased cardiovascular disease risk associated with T1D.",
keywords = "apolipoproteins, endothelium, lipoproteins, sphingolipids, tumor necrosis factor-alpha",
author = "Cecilia Frej and Mendez, {Armando J.} and {Ruiz Garcia}, Mario and Melanie Castillo and Hughes, {Thomas A.} and Bj{\"o}rn Dahlb{\"a}ck and Goldberg, {Ronald B.}",
year = "2017",
month = jun,
day = "1",
doi = "10.1161/ATVBAHA.117.309275",
language = "English",
volume = "37",
pages = "1194--1205",
journal = "Arteriosclerosis, Thrombosis and Vascular Biology",
issn = "1524-4636",
publisher = "Lippincott Williams & Wilkins",
number = "6",

}