< Previous         Next >  
HDL quality features revealed by proteome‒lipidome connectivity are associated with atherosclerotic disease
Dandan Wang1,† , Bilian Yu2,† , Qingrun Li1,† , Yanhong Guo3,† , Tomonari Koike3 , Yui Koike3 , Qingqing Wu1 , Jifeng Zhang3 , Ling Mao2 , Xiaoyu Tang2 , Liang Sun4 , Xu Lin4 , Jiarui Wu1,5 , Y. Eugene Chen3,* , Daoquan Peng2,* , Rong Zeng1,5,*
1CAS 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
2Department of Cardiovascular Medicine, the Second Xiangya Hospital, Central South University, Changsha 410011, China
3Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
4Key Laboratory of Nutrition and Metabolism, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China
5CAS Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310024, China
These authors contributed equally to this work
*Correspondence to:Y. Eugene Chen , Daoquan Peng ,; Rong Zeng ,
J Mol Cell Biol, Volume 14, Issue 3, March 2022, mjac004,
Keyword: HDL, high resolution, proteomics, lipidomics, atherosclerotic disease

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.