Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.
Backgound: 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 disea...
| Publicado en: | Circulation Vol. 137; no. 25; pp. 2741 - 2757 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
6/19/2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=130220529&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 130220529 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00097322 1FV jtl: Circulation issn: 00097322 maglogo: N pubinfo: dt: 6/19/2018 vid: 137 iid: 25 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 130220529 130220529 NLM29915101 130220529 10.1161/CIRCULATIONAHA.118.034365 NLM29915101 130220529 ppf: 2741 ppct: 16 formats: tig: atl: Proteomic Architecture of Human Coronary and Aortic Atherosclerosis. aug: au: Herrington, David M. Mao, Chunhong Parker, Sarah J. Fu, Zongming Yu, Guoqiang Chen, Lulu Venkatraman, Vidya Fu, Yi Wang, Yizhi Howard, Timothy D. Jun, Goo Zhao, Caroline F. Liu, Yongmei Saylor, Georgia Spivia, Weston R. Athas, Grace B. Troxclair, Dana Hixson, James E. Vander Heide, Richard S. Wang, Yue affil: Section on Cardiovascular Medicine, Department of Internal Medicine sug: subj: Proteomics Methods Coronary Arteriosclerosis Metabolism Aorta Coronary Vessels Aortic Diseases Metabolism Proteins Analysis Mass Spectrometry Atherosclerosis Metabolism Aortic Diseases Pathology Atherosclerosis Human Young Adult Middle Age Coronary Vessels Pathology Male Atherosclerosis Pathology Adult Autopsy Metabolic Networks and Pathways Aorta Pathology Adolescence Female Coronary Arteriosclerosis Pathology Validation Studies Comparative Studies Evaluation Research Multicenter Studies Middle Aged: 45-64 years Adult: 19-44 years Adolescent: 13-18 years Male Female ab: Backgound: 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.Methods: Here we describe the human arterial proteome and 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 rewiring, and likely regulatory features of the protein networks associated with early atherosclerosis and how they vary across 2 anatomic distributions.Results: The data document significant differences in mitochondrial protein abundance between coronary and aortic samples (coronary>>aortic), and between atherosclerotic and normal tissues (atherosclerotic<<normal), and major alterations in tumor necrosis factor, insulin receptor, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-γ protein networks, as well, in the setting of early disease. In addition, a subset of tissue protein biomarkers indicative of early atherosclerosis was shown to predict anatomically defined coronary atherosclerosis when measured in plasma samples in a separate clinical cohort (area under the curve=0.92 [0.83-0.96]), thereby validating the use of human tissue proteomics to discover relevant plasma biomarkers for clinical applications. In addition to the specific proteins and pathways identified here, the publicly available data resource and the analysis pipeline used illustrate a strategy for interrogating and interpreting the proteomic architecture of tissues that may be relevant for other chronic diseases characterized by multicellular tissue phenotypes.Conclusions: The human arterial proteome can be viewed as a complex network whose architectural features vary considerably as a function of anatomic location and the presence or absence of atherosclerosis. The data suggest important reductions in mitochondrial protein abundance in early atherosclerosis and also identify a subset of plasma proteins that are highly predictive of angiographically defined coronary disease. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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