High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus

Lower plasma levels of high-density lipoproteins (HDL) in adolescents with type 2 diabetes (T2D) have been associated with a higher pulse wave velocity (PWV), a marker of arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered in T2D and these may drive these relat...

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Main Authors: Xiaoting Zhu, Amy S. Shah, Debi K. Swertfeger, Hailong Li, Sheng Ren, John T. Melchior, Scott M. Gordon, W. Sean Davidson, L. Jason Lu
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Complexity
Online Access:http://dx.doi.org/10.1155/2018/7514709
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author Xiaoting Zhu
Amy S. Shah
Debi K. Swertfeger
Hailong Li
Sheng Ren
John T. Melchior
Scott M. Gordon
W. Sean Davidson
L. Jason Lu
author_facet Xiaoting Zhu
Amy S. Shah
Debi K. Swertfeger
Hailong Li
Sheng Ren
John T. Melchior
Scott M. Gordon
W. Sean Davidson
L. Jason Lu
author_sort Xiaoting Zhu
collection DOAJ
description Lower plasma levels of high-density lipoproteins (HDL) in adolescents with type 2 diabetes (T2D) have been associated with a higher pulse wave velocity (PWV), a marker of arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered in T2D and these may drive these relationships. In this work, we set out to reveal any specific proteins and subspecies that are related to arterial stiffness in youth with T2D from proteomics data. Plasma and PWV measurements were previously acquired from lean and T2D adolescents. Each plasma sample was separated into 18 fractions and evaluated by mass spectrometry. Then, we applied a validated network-based computational approach to reveal HDL subspecies associated with PWV. Among 68 detected phospholipid-associated proteins, we found that seven were negatively correlated with PWV, indicating that they may be atheroprotective. Conversely, nine proteins show positive correlation with PWV, suggesting that they may be related to arterial stiffness. Intriguingly, our results demonstrate that apoA-I and histidine-rich glycoprotein may reverse their protective roles and become antagonistic in the setting of T2D. Furthermore, we revealed two arterial stiffness-associated HDL subspecies, each of which contains multiple PWV-related proteins. Correlation and disease association analyses suggest that these HDL subspecies might link T2D to its cardiovascular-related complications.
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spelling doaj-art-e3804fd74de941ae92c52b8357d5436c2025-08-20T02:21:21ZengWileyComplexity1076-27871099-05262018-01-01201810.1155/2018/75147097514709High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes MellitusXiaoting Zhu0Amy S. Shah1Debi K. Swertfeger2Hailong Li3Sheng Ren4John T. Melchior5Scott M. Gordon6W. Sean Davidson7L. Jason Lu8School of Information Management, Wuhan University, Wuhan 430072, ChinaDivision of Endocrinology, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, MLC 7012, Cincinnati, OH 45229-3039, USADivision of Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, OH 45229-3039, USADivision of Neonatology and Pulmonary Biology, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USADivision of Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, OH 45229-3039, USADepartment of Pathology and Laboratory Medicine, Division of Experimental Pathology, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, OH 45237-0507, USALipoprotein Metabolism Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USADepartment of Pathology and Laboratory Medicine, Division of Experimental Pathology, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, OH 45237-0507, USADivision of Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, OH 45229-3039, USALower plasma levels of high-density lipoproteins (HDL) in adolescents with type 2 diabetes (T2D) have been associated with a higher pulse wave velocity (PWV), a marker of arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered in T2D and these may drive these relationships. In this work, we set out to reveal any specific proteins and subspecies that are related to arterial stiffness in youth with T2D from proteomics data. Plasma and PWV measurements were previously acquired from lean and T2D adolescents. Each plasma sample was separated into 18 fractions and evaluated by mass spectrometry. Then, we applied a validated network-based computational approach to reveal HDL subspecies associated with PWV. Among 68 detected phospholipid-associated proteins, we found that seven were negatively correlated with PWV, indicating that they may be atheroprotective. Conversely, nine proteins show positive correlation with PWV, suggesting that they may be related to arterial stiffness. Intriguingly, our results demonstrate that apoA-I and histidine-rich glycoprotein may reverse their protective roles and become antagonistic in the setting of T2D. Furthermore, we revealed two arterial stiffness-associated HDL subspecies, each of which contains multiple PWV-related proteins. Correlation and disease association analyses suggest that these HDL subspecies might link T2D to its cardiovascular-related complications.http://dx.doi.org/10.1155/2018/7514709
spellingShingle Xiaoting Zhu
Amy S. Shah
Debi K. Swertfeger
Hailong Li
Sheng Ren
John T. Melchior
Scott M. Gordon
W. Sean Davidson
L. Jason Lu
High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus
Complexity
title High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus
title_full High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus
title_fullStr High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus
title_full_unstemmed High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus
title_short High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus
title_sort high density lipoproteins associated proteins and subspecies related to arterial stiffness in young adults with type 2 diabetes mellitus
url http://dx.doi.org/10.1155/2018/7514709
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