Dataset Information

Proteomic landscape of human coronary artery atherosclerosis.

ABSTRACT: In order to investigate novel biomarkers for the detection of coronary artery disease for effective therapeutic targets, a comprehensive understanding of the protein networks and protein expression abundance in coronary artery samples is required. This was established by means of liquid chromatography (LC)?mass spectrometry (MS)/MS analysis in the present study. A total of 20 human coronary artery specimens from 2 autopsied adults were employed in the present study. The natural history and histological classification of the atherosclerotic lesions of the coronary artery samples were analyzed by hematoxylin and eosin (H&E) staining, and the human coronary arterial proteome and proteomics features were characterized by MS analysis. The present study identified 2,135 proteins in the 20 coronary artery segments samples from the 2 cases. Combined with the results of H&E staining of the coronary artery samples, a total of 174 proteins, including 4 upregulated proteins and 164 downregulated proteins (excluding 6 proteins with inconsistent expression tendencies), were shown to be associated with coronary artery disease. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of the differentially expressed proteins revealed that the mitochondrial energy metabolism may be responsible for the occurrence and development of coronary artery atherosclerosis. The human coronary arterial proteome can be considered as a complex network whose architectural characteristics vary considerably as a function of the presence or absence, and histological classification of coronary artery atherosclerosis. These data thus suggest that the prevention of mitochondrial dysfunction via the retrieval of the mitochondrial associated proteins expression may be a promising target in coronary artery disease.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC7255452 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Proteomic landscape of human coronary artery atherosclerosis.

Zhou Yaqing Y Yuan Jinxia J Fan Yinwen Y An Fenghui F Chen Jiaxin J Zhang Yongjie Y Jin Jianliang J Gu Mufeng M Mao Zhiyuan Z Sun Haijian H Jia Qiaowei Q Zhao Chenhui C Ji Mingyue M Zhang Jing J Xu Guangxu G Jia Enzhi E

International journal of molecular medicine 20200512 1

In order to investigate novel biomarkers for the detection of coronary artery disease for effective therapeutic targets, a comprehensive understanding of the protein networks and protein expression abundance in coronary artery samples is required. This was established by means of liquid chromatography (LC)‑mass spectrometry (MS)/MS analysis in the present study. A total of 20 human coronary artery specimens from 2 autopsied adults were employed in the present study. The natural history and histo ...[more]

PMID: 32626919

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Project description:BackgoundThe 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.MethodsHere 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.ResultsThe 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.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.

Dataset Information

Proteomic landscape of human coronary artery atherosclerosis.

Publications

Proteomic landscape of human coronary artery atherosclerosis.

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