HDL quality features revealed by proteome‒lipidome connectivity are associated with atherosclerotic disease

Author:

Wang Dandan1,Yu Bilian2,Li Qingrun1,Guo Yanhong3,Koike Tomonari3,Koike Yui3,Wu Qingqing1ORCID,Zhang Jifeng3,Mao Ling2,Tang Xiaoyu2,Sun Liang4,Lin Xu4,Wu Jiarui15,Chen Y Eugene3ORCID,Peng Daoquan2,Zeng Rong15

Affiliation:

1. CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences , Shanghai 200031, China

2. Department of Cardiovascular Medicine, the Second Xiangya Hospital, Central South University , Changsha 410011, China

3. Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center , Ann Arbor, MI 48109, USA

4. Key Laboratory of Nutrition and Metabolism, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences , Shanghai 200031, China

5. CAS Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Hangzhou 310024, China

Abstract

Abstract Lipoprotein, especially high-density lipoprotein (HDL), particles are composed of multiple heterogeneous subgroups containing various proteins and lipids. The molecular distribution among these subgroups is closely related to cardiovascular disease (CVD). Here, we established high-resolution proteomics and lipidomics (HiPL) methods to depict the molecular profiles across lipoprotein (Lipo-HiPL) and HDL (HDL-HiPL) subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level. Furthermore, based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups, we achieved the relationship of proteome‒lipidome connectivity (PLC) for lipoprotein and HDL particles. By application of these methods to high-fat, high-cholesterol diet-fed rabbits and acute coronary syndrome (ACS) patients, we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles. Of note, the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method, suggesting their potential in ACS diagnosis. Together, we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.

Funder

Center for Alcohol Studies

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Genetics,Molecular Biology,General Medicine

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