Dataset Information

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.

ABSTRACT:

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<ConclusionsThe 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.

SUBMITTER: Herrington DM

PROVIDER: S-EPMC6011234 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.

Herrington David M DM Mao Chunhong C Parker Sarah J SJ Fu Zongming Z Yu Guoqiang G Chen Lulu L Venkatraman Vidya V Fu Yi Y Wang Yizhi Y Howard Timothy D TD Jun Goo G Zhao Caroline F CF Liu Yongmei Y Saylor Georgia G Spivia Weston R WR Athas Grace B GB Troxclair Dana D Hixson James E JE Vander Heide Richard S RS Wang Yue Y Van Eyk Jennifer E JE

Circulation 20180601 25

<h4>Backgound</h4>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.<h4>Methods</h4>Here we describe the human arterial proteome and proteomic features strongly associated with early atherosclerosis based on mass sp ...[more]

PMID: 29915101

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Project description:Thoracic aortic calcification (TAC) and coronary artery calcification (CAC) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. In a population-based cohort study, 3270 participants (aged 45-74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow-up of 5.1±0.3 years for quantification of calcification of the ascending (ATAC) and descending thoracic aorta (DTAC) and CAC. Multivariable relative risk regression analysis was used to investigate associations of cardiovascular risk factors with incident TAC, of baseline TAC with incident CAC, and of baseline CAC with incident TAC. Of 1243 participants with baseline TAC of 0, 517 (41.6%) revealed incident TAC after 5 years. Incidence of descending TAC was higher (34.5%) than ascending TAC (23.3%). Incident TAC after 5 years was associated with age (relative risk 1.26 [95% CI 1.21-1.33], per 5 years), blood pressure (relative risk 1.06 [95% CI 1.03-1.10], per 10 mm Hg), low-density lipoprotein cholesterol (relative risk 1.08 [95% CI 1.04-1.12], per 20 mg/dL), and smoking (relative risk 1.28 [95% CI 1.07-1.53]). Among the 1185 participants without CAC at baseline, the risk of developing CAC was 28.3% when baseline TAC was present compared with 22.2% among those without baseline TAC (excess risk 6.1% [95% CI 1.2-11.0%]). The point estimate of excess risk for incident CAC was higher for ascending TAC (10.8% [95% CI 4.8-16.7%]) and low for descending TAC (1.8% [95% CI -3.2% to 6.7%]). Excess risk for developing ascending and descending TAC with present baseline CAC was 16.4% (95% CI 12.7-20.0%) and 15.6% (95% CI 10.8-20.4%), respectively. TAC and CAC share similar major determinants for incident calcification. Participants with TAC, especially ascending TAC, are at elevated risk for development of CAC.

Dataset Information

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.

Backgound

Methods

Results

Publications

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.

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