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Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study

BACKGROUND: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctiona...

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Autores principales: Gourgari, Evgenia, Ma, Junfeng, Playford, Martin P., Mehta, Nehal N., Goldman, Radoslav, Remaley, Alan T., Gordon, Scott M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437869/
https://www.ncbi.nlm.nih.gov/pubmed/30922315
http://dx.doi.org/10.1186/s12933-019-0846-9
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author Gourgari, Evgenia
Ma, Junfeng
Playford, Martin P.
Mehta, Nehal N.
Goldman, Radoslav
Remaley, Alan T.
Gordon, Scott M.
author_facet Gourgari, Evgenia
Ma, Junfeng
Playford, Martin P.
Mehta, Nehal N.
Goldman, Radoslav
Remaley, Alan T.
Gordon, Scott M.
author_sort Gourgari, Evgenia
collection PubMed
description BACKGROUND: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. METHODS: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. RESULTS: Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P < 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P < 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. CONCLUSIONS: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-019-0846-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-64378692019-04-08 Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study Gourgari, Evgenia Ma, Junfeng Playford, Martin P. Mehta, Nehal N. Goldman, Radoslav Remaley, Alan T. Gordon, Scott M. Cardiovasc Diabetol Original Investigation BACKGROUND: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. METHODS: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. RESULTS: Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P < 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P < 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. CONCLUSIONS: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-019-0846-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-28 /pmc/articles/PMC6437869/ /pubmed/30922315 http://dx.doi.org/10.1186/s12933-019-0846-9 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Gourgari, Evgenia
Ma, Junfeng
Playford, Martin P.
Mehta, Nehal N.
Goldman, Radoslav
Remaley, Alan T.
Gordon, Scott M.
Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study
title Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study
title_full Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study
title_fullStr Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study
title_full_unstemmed Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study
title_short Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study
title_sort proteomic alterations of hdl in youth with type 1 diabetes and their associations with glycemic control: a case–control study
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437869/
https://www.ncbi.nlm.nih.gov/pubmed/30922315
http://dx.doi.org/10.1186/s12933-019-0846-9
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