Percutaneous coronary intervention-induced plaque disruption led to a 1.44-fold increase in systemic lipopolysaccharide binding protein levels, identifying it as a novel biomarker of plaque rupture.
Observational (n=81)
No
Does a workflow combining plaque imaging and proteomics identify biomarkers of human coronary atherosclerotic plaque disruption?
A novel workflow integrating optical coherence tomography and proteomics identified new biomarkers, including MMP9 and five novel proteins, associated with human coronary plaque disruption.
Effect estimate: 1.44 times increase (95% CI 1.07-1.81)
p-value: p=0.0159
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.
Lee et al. (Mon,) conducted a observational in Coronary atherosclerosis (n=81). Percutaneous coronary intervention (PCI) vs. Diagnostic angiography without stenting was evaluated on Plasma lipopolysaccharide binding protein (LBP) levels (1.44 times increase, 95% CI 1.07-1.81, p=0.0159). Percutaneous coronary intervention-induced plaque disruption led to a 1.44-fold increase in systemic lipopolysaccharide binding protein levels, identifying it as a novel biomarker of plaque rupture.