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Live Observation of Atherosclerotic Plaque Disruption in Apolipoprotein E-Deficient Mouse.

ABSTRACT: The actual occurrence of spontaneous plaque rupture in mice has been a matter of debate. We report on an in vivo observation of the actual event of possible plaque disruption in a living ApoE(-/-) mouse.During live contrast-enhanced ultrasonography of a 50-week-old ApoE(-/-) male mouse, symptoms suggesting plaque disruption in the brachiocephalic artery were observed. Histological analysis confirmed the presence of advanced atherosclerotic lesions with dissections and intraplaque hemorrhage in the affected brachiocephalic trunk, pointing towards plaque rupture as the cause of the observed event. However, we did not detect a luminal thrombus or cap rupture, which is a key criterion for plaque rupture in human atherosclerosis.This study reports the real-time occurrence of a possible plaque rupture in a living ApoE(-/-) mouse.

SUBMITTER: Daeichin V

PROVIDER: S-EPMC5023208 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

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Live Observation of Atherosclerotic Plaque Disruption in Apolipoprotein E-Deficient Mouse.

Daeichin V V Sluimer J C JC van der Heiden K K Skachkov I I Kooiman K K Janssen A A Janssen B B Bosch J G JG de Jong N N Daemen M J A P MJ van der Steen A F W AF

Ultrasound international open 20151101 2

<h4>Aim</h4>The actual occurrence of spontaneous plaque rupture in mice has been a matter of debate. We report on an in vivo observation of the actual event of possible plaque disruption in a living ApoE(-/-) mouse.<h4>Methods and results</h4>During live contrast-enhanced ultrasonography of a 50-week-old ApoE(-/-) male mouse, symptoms suggesting plaque disruption in the brachiocephalic artery were observed. Histological analysis confirmed the presence of advanced atherosclerotic lesions with dis ...[more]

PMID: 27689156

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Project description: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.

Dataset Information

Live Observation of Atherosclerotic Plaque Disruption in Apolipoprotein E-Deficient Mouse.

Publications

Live Observation of Atherosclerotic Plaque Disruption in Apolipoprotein E-Deficient Mouse.

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