Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

ABSTRACT: Peripheral blood RNA-Seq from human coronary artery calcification cases and controls; Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques. Eight cases and eight controls (matched for gender, age and ancestry); RNA sequencing of peripheral blood from a discovery set of eight CAC cases and eight matched controls was used to identify dysregulated genes, which were validated using the NanoString® and Affymetrix GeneChip® Human Exon ST Array platforms. The median CAC scores for cases in the screening and validation sets were 1531.5 and 668.5, respectively, while all controls had a score of zero.

ORGANISM(S): Homo sapiens

SUBMITTER: Shurjo Sen

PROVIDER: E-GEOD-58150 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrative DNA, RNA, and protein evidence connects TREML4 to coronary artery calcification.

Sen Shurjo K SK Boelte Kimberly C KC Barb Jennifer J JJ Joehanes Roby R Zhao XiaoQing X Cheng Qi Q Adams Lila L Teer Jamie K JK Accame David S DS Chowdhury Soma S Singh Larry N LN Kavousi Maryam M Peyser Patricia A PA Quigley Laura L Priel Debra Long DL Lau Karen K Kuhns Douglas B DB Yoshimura Teizo T Johnson Andrew D AD Hwang Shih-Jen SJ Chen Marcus Y MY Arai Andrew E AE Green Eric D ED Mullikin James C JC Kolodgie Frank D FD O'Donnell Christopher J CJ Virmani Renu R Munson Peter J PJ McVicar Daniel W DW Biesecker Leslie G LG

American journal of human genetics 20140626 1

Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy by using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques. RNA sequencing of peripheral blood from a discovery set of CAC c ...[more]

PMID: 24975946

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Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Dataset Information

Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

Publications

Integrative DNA, RNA, and protein evidence connects TREML4 to coronary artery calcification.

Similar Datasets

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