Journal
CLINICAL PROTEOMICS
Volume 14, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12014-017-9157-x
Keywords
Coronary atherosclerosis; Plaque rupture; Proteomics; Biomarkers
Categories
Funding
- Royal Australasian College of Surgeons Scholarship Program
- Academy of Medical Sciences UK
- Kennedy Trust Award
- Wellcome Trust Award [105605/Z/14Z]
- National Institute of Health Research (NIHR) Oxford Biomedical Research Centre
- British Heart Foundation Oxford Centre of Research Excellence [RG/13/1/30181]
- Chair Award [CH/16/1/32013]
- British Heart Foundation [RG/17/10/32859, FS/16/15/32047] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10166] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15SA0018346, NNF15SA0018486] Funding Source: researchfish
Ask authors/readers for more resources
Background: Atherosclerotic plaque rupture is the culprit event which underpins most acute vascular syndromes such as acute myocardial infarction. Novel biomarkers of plaque rupture could improve biological understanding and clinical management of patients presenting with possible acute vascular syndromes but such biomarker(s) remain elusive. Investigation of biomarkers in the context of de novo plaque rupture in humans is confounded by the inability to attribute the plaque rupture as the source of biomarker release, as plaque ruptures are typically associated with prompt down-stream events of myocardial necrosis and systemic inflammation. Methods: We developed a novel approach to identify potential biomarkers of plaque rupture by integrating plaque imaging, using optical coherence tomography, with both plaque and plasma proteomic analysis in a human model of angioplasty-induced plaque disruption. Results: We compared two pairs of coronary plaque debris, captured by a FilterWire Device, and their corresponding control samples and found matrix metalloproteinase 9 (MMP9) to be significantly enriched in plaque. Plaque contents, as defined by optical coherence tomography, affect the systemic changes of MMP9. Disruption of lipid-rich plaque led to prompt elevation of plasma MMP9, whereas disruption of non-lipid-rich plaque resulted in delayed elevation of plasma MMP9. Systemic MMP9 elevation is independent of the associated myocardial necrosis and systemic inflammation (measured by Troponin I and C-reactive protein, respectively). This information guided the selection of a subset of subjects of for further label free proteomics analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). We discovered five novel, plaque-enriched proteins (lipopolysaccharide binding protein, Annexin A5, eukaryotic translocation initiation factor, syntaxin 11, cytochrome B5 reductase 3) to be significantly elevated in systemic circulation at 5 min after plaque disruption. Conclusion: This novel approach for biomarker discovery in human coronary artery plaque disruption can identify new biomarkers related to human coronary artery plaque composition and disruption.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available