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Proteomic Architecture of Human Coronary and Aortic Atherosclerosis

By M Herrington David, Mao Chunhong, Parker Sarah, Fu ZongminG, Yu Guoqiang, Chen Lulu, Venkatraman Vidya, Fu Yi, Wang Yizhi, Howard Tim, Goo Jun, CF Zhao, Liu Yongming, Saylor Georgia, Athas Grace, Troxclair Dana, Hixson James, Vander Heide Richard, Wang Yue, Van Eyk Jennifer

Posted 29 Jun 2017
bioRxiv DOI: 10.1101/157248 (published DOI: 10.1161/circulationaha.118.034365)

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.

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