Proteomics in atherosclerosis

Martinez-Pinna, Roxana; Martin-Ventura, José Luis; Mas, Sebastián; Blanco-Colio, Luís Miguel; Tuñón, José; Egido, Jesús

doi:10.1007/s11883-008-0033-z

Cited by 11 publications

(12 citation statements)

References 26 publications

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“…Over the last few years, proteomics has been used extensively for the discovery of potential biomarkers for cancer (32), atherosclerosis (33), and cardiovascular disease (for reviews, see Refs. 9 and 34).…”

Section: Cmybp-c As a Candidate Marker Of Myocardial Infarctionmentioning

confidence: 99%

Identification of Cardiac Myosin-binding Protein C as a Candidate Biomarker of Myocardial Infarction by Proteomics Analysis

Jacquet¹,

Yin²,

Sicard³

et al. 2009

Molecular & Cellular Proteomics

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Acute myocardial infarction (AMI) is a common cause of death for which effective treatments are available provided that diagnosis is rapid. The current diagnostic gold standards are circulating cardiac troponins I and T. However, their slow release delays diagnosis, and their persistence limits their utility in the identification of reinfarction. The aim was to identify candidate biomarkers of AMI. Isolated mouse hearts were perfused with oxygenated protein-free buffer, and coronary effluent was collected after ischemia or during matched normoxic perfusion. Effluents were analyzed using proteomics approaches based on one-or two-dimensional initial separation. Of the 459 proteins identified after ischemia with one-dimensional separation, 320 were not detected in the control coronary effluent. Among these were all classic existing biomarkers of AMI. We also identified the cardiac isoform of myosin-binding protein C in its full-length form and as a 40-kDa degradation product. This protein was not detected in the other murine organs examined, increased markedly with even trivial myocardial infarction, and could be detected in the plasma after myocardial infarction in vivo, a profile compatible with a biomarker of AMI. Two-dimensional fluorescence DIGE of ischemic and control coronary effluents identified more than 200 asymmetric spots verified by swapping dyes. Once again existing biomarkers of injury were confirmed as well as posttranslational modifications of antioxidant proteins such as peroxiredoxins. Perfusing hearts with protein-free buffers provides a platform of graded ischemic injury that allows detailed analysis of protein release and identification of candidate cardiac biomarkers like myosin-binding protein C.

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Section: Cmybp-c As a Candidate Marker Of Myocardial Infarctionmentioning

confidence: 99%

Identification of Cardiac Myosin-binding Protein C as a Candidate Biomarker of Myocardial Infarction by Proteomics Analysis

Jacquet¹,

Yin²,

Sicard³

et al. 2009

Molecular & Cellular Proteomics

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“…The normal biological variation in protein expression among cells of identical lineage is around 15% to 30% (15). Under situations of stress or in tumors, an even higher variation of protein expression is expected (15,16). A major source of this expressional variation is caused by differences in the structure and function of different cell populations present in individual samples.…”

Section: Discussionmentioning

confidence: 99%

A Proteome Comparison Between Physiological Angiogenesis and Angiogenesis in Glioblastoma

Mustafa

Dekker²,

Stingl³

et al. 2012

Molecular & Cellular Proteomics

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The molecular pathways involved in neovascularization of regenerating tissues and tumor angiogenesis resemble each other. However, the regulatory mechanisms of neovascularization under neoplastic circumstances are unbalanced leading to abnormal protein expression patterns resulting in the formation of defective and often abortive tumor vessels. Because gliomas are among the most vascularized tumors, we compared the protein expression profiles of proliferating vessels in glioblastoma with those in tissues in which physiological angiogenesis takes place. By using a combination of laser microdissection and LTQ Orbitrap mass spectrometry comparisons of protein profiles were made. The approach yielded 29 and 12 differentially expressed proteins for glioblastoma and endometrium blood vessels, respectively. The aberrant expression of five proteins, i.e. periostin, tenascin-C, TGFbeta induced protein, integrin alpha-V, and laminin subunit beta-2 were validated by immunohistochemistry. In addition, pathway analysis of the differentially expressed proteins was performed and significant differences in the usage of angiogenic pathways were found. We conclude that there are essential differences in protein expression profiles between tumor and normal physiological angiogenesis. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.008466, 1-9, 2012.Neovascularization is a complex process taking place under physiological and pathological circumstances. There is large overlap in the cellular components, regulatory factors, and signaling mechanisms acting in the angiogenic process of regeneration, embryonic development, and tumor vascularization (1). In both physiological and pathological neovascularization signaling mechanisms, growth factors and their receptors, cell adhesion molecules and their specific extracellular matrix ligands take part (2). Angiocrine molecules like basic fibroblast growth factor and vascular endothelial growth factor and their receptors have been identified in the context of physiological and tumor angiogenesis (3). It is believed that the angiogenic switch is always triggered by hypoxia, starting with the up-regulation of vascular endothelial growth factor. The process of neovascularization consists not only of sprouting angiogenesis, but also of activation of endothelial precursor cells with the capacity to form de novo blood vessels (vasculogenesis). Vasculogenesis is also part of tumor vascularization but there is dispute about its relative importance (4, 5). Despite the similarities there are obvious differences between physiological vascularization and angiogenesis in tumors. Under physiological conditions, the regulatory mechanisms are well-coordinated and balanced and endothelial cell functions are tightly orchestrated by both pro-and anti-angiogenic factors. In tumor angiogenesis however, there is an excess of pro-angiogenic factors leading to uncoordinated proliferation and tubulogenesis of endothelial cells and migration of mural cells like pericytes (6). It is likely that the molecular diff...

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“…Proteomics emerged as a technique to complement the information given by genomic analysis in biological processes. It was created to overcome the limitations of genomics associated with the fact that genetic expression is not always related to a particular protein or peptidic end-product refl ecting a physiological or pathological process within the cell or tissue (13). For example, a particular DNA segment can produce different proteins by a phenomenon called alternative splicing.…”

Section: Definitions and Methodology Of Genomics Proteomics And Metmentioning

confidence: 99%

The role of genomics and proteomics in identifying subjects at risk of clinical manifestations of coronary atherosclerosis and their future clinical applications

Alviar¹,

Moreno²

2012

Coronary Atherosclerosis

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OUTLINEGenomic medicine has provided tremendous advantage in the identifi cation of subjects at increased risk of cardiovascular disease, in particular atherosclerotic heart disease. Several genes and loci have been identifi ed with the use of advanced technologies, while signifi cant scientifi c efforts are currently being directed towards the investigation of these and other markers. In the same way, proteomics and metabolomics research have provided considerable evidence about specifi c biomarkers that are linked to atherosclerosis. In this chapter we will fi rst provide an overview of the different techniques in genomics and proteomics that are currently being used in biomedical research and their applications in cardiovascular medicine. Then, we will describe specifi c genetic markers linked to coronary atherosclerosis with a review of the evidence behind them. Finally we will review the proteomic markers associated with higher risk of coronary heart disease and we will discuss those biomarkers that have the most robust evidence as risk factors of coronary atherosclerosis, and the limitations in the interpretation of proteomics in atherosclerosis.

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Proteomics in atherosclerosis

Cited by 11 publications

References 26 publications

Identification of Cardiac Myosin-binding Protein C as a Candidate Biomarker of Myocardial Infarction by Proteomics Analysis

Identification of Cardiac Myosin-binding Protein C as a Candidate Biomarker of Myocardial Infarction by Proteomics Analysis

A Proteome Comparison Between Physiological Angiogenesis and Angiogenesis in Glioblastoma

The role of genomics and proteomics in identifying subjects at risk of clinical manifestations of coronary atherosclerosis and their future clinical applications

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