Table of Contents Author Guidelines Submit a Manuscript
Volume 2018, Article ID 7514709, 14 pages
Research Article

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

1School of Information Management, Wuhan University, Wuhan 430072, China
2Division of Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, OH 45229-3039, USA
3Division of Endocrinology, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, MLC 7012, Cincinnati, OH 45229-3039, USA
4Division of Neonatology and Pulmonary Biology, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
5Department of Pathology and Laboratory Medicine, Division of Experimental Pathology, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, OH 45237-0507, USA
6Lipoprotein Metabolism Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

Correspondence should be addressed to L. Jason Lu; gro.cmhcc@ul.gnol

Received 25 August 2017; Accepted 11 January 2018; Published 8 March 2018

Academic Editor: Mirjana Popović

Copyright © 2018 Xiaoting Zhu et al. 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.


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.