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
(2017) In Arteriosclerosis, Thrombosis, and Vascular Biology 37(6). p.1194-1205- 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.... (More)
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.
(Less)
- author
- Frej, Cecilia LU ; Mendez, Armando J. ; Ruiz Garcia, Mario LU ; Castillo, Melanie ; Hughes, Thomas A. ; Dahlbäck, Björn LU and Goldberg, Ronald B.
- organization
- publishing date
- 2017-06-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- apolipoproteins, endothelium, lipoproteins, sphingolipids, tumor necrosis factor-alpha
- in
- Arteriosclerosis, Thrombosis, and Vascular Biology
- volume
- 37
- issue
- 6
- pages
- 1194 - 1205
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85019732203
- pmid:28385702
- wos:000401947700025
- ISSN
- 1079-5642
- DOI
- 10.1161/ATVBAHA.117.309275
- language
- English
- LU publication?
- yes
- id
- 8c2aee10-537e-4512-b77d-f63d3e34a5da
- date added to LUP
- 2017-06-19 10:45:53
- date last changed
- 2024-02-29 16:57:19
@article{8c2aee10-537e-4512-b77d-f63d3e34a5da,
abstract = {{<p>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 S1P<sub>1</sub>-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.</p>}},
author = {{Frej, Cecilia and Mendez, Armando J. and Ruiz Garcia, Mario and Castillo, Melanie and Hughes, Thomas A. and Dahlbäck, Björn and Goldberg, Ronald B.}},
issn = {{1079-5642}},
keywords = {{apolipoproteins; endothelium; lipoproteins; sphingolipids; tumor necrosis factor-alpha}},
language = {{eng}},
month = {{06}},
number = {{6}},
pages = {{1194--1205}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Arteriosclerosis, Thrombosis, and Vascular Biology}},
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}},
url = {{http://dx.doi.org/10.1161/ATVBAHA.117.309275}},
doi = {{10.1161/ATVBAHA.117.309275}},
volume = {{37}},
year = {{2017}},
}