RT Journal Article
SR Electronic
T1 Proteomic Architecture of Human Coronary and Aortic Atherosclerosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 157248
DO 10.1101/157248
A1 M Herrington David
A1 Mao Chunhong
A1 Parker Sarah
A1 Fu ZongminG
A1 Yu Guoqiang
A1 Chen Lulu
A1 Venkatraman Vidya
A1 Fu Yi
A1 Wang Yizhi
A1 Howard Tim
A1 Goo Jun
A1 CF Zhao
A1 Liu Yongming
A1 Saylor Georgia
A1 Athas Grace
A1 Troxclair Dana
A1 Hixson James
A1 Vander Heide Richard
A1 Wang Yue
A1 Van Eyk Jennifer
YR 2017
UL http://biorxiv.org/content/early/2017/06/29/157248.abstract
AB The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets. Here we describe the human arterial proteome and the proteomic features strongly associated with early atherosclerosis based on mass-spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling and bioinformatic analyses defined the composition, network re-wiring and likely regulatory features of the protein networks associated with early atherosclerosis. Among other things the results reveal major differences in mitochondrial protein mass between the coronary artery and distal aorta in both normal and atherosclerotic samples – highlighting the importance of anatomic specificity and dynamic network structures in in the study of arterial proteomics. The publicly available data resource and the description of the analysis pipeline establish a new foundation for understanding the proteomic architecture of atherosclerosis and provide a template for similar investigations of other chronic diseases characterized by multi-cellular tissue phenotypes.HighlightsLC MS/MS analysis performed on 200 human aortic or coronary artery samplesNumerous proteins, networks, and regulatory pathways associated with early atherosclerosisMitochondrial proteins mass and selected metabolic regulatory pathways vary dramatically by disease status and anatomic locationPublically available data resource and analytic pipeline are provided or described in detail