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Percutaneous Sampling of Local Biomolecule Gradients Across Coronary Artery Atherosclerotic Plaques.

ABSTRACT: A percutaneous catheter device, the Liquid Biopsy System, was developed to sample the unstirred boundary layer of blood upstream and downstream of intact and disrupted human coronary atherosclerotic plaques. Using multiplexed proximity extension assays, release of 20 biomolecules was simultaneously detected in samples taken across plaques before balloon angioplasty, including the soluble form of the endothelial lectin-like oxidized LDL receptor. Additional biomolecules, including matrix metalloproteinase-12, were released after plaque disruption with angioplasty. These experiments demonstrate the power of the Liquid Biopsy System to yield new scientific insights and its ultimate potential to generate new biomarkers and surrogate endpoints for clinical trials.

SUBMITTER: West NEJ

PROVIDER: S-EPMC6058996 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Percutaneous Sampling of Local Biomolecule Gradients Across Coronary Artery Atherosclerotic Plaques.

West Nick E J NEJ Corrigan Joseph P JP Owen Richard H G RHG Hoole Stephen P SP Brown Adam J AJ Blatcher Stephen S Newby Andrew C AC

JACC. Basic to translational science 20171225 6

A percutaneous catheter device, the Liquid Biopsy System, was developed to sample the unstirred boundary layer of blood upstream and downstream of intact and disrupted human coronary atherosclerotic plaques. Using multiplexed proximity extension assays, release of 20 biomolecules was simultaneously detected in samples taken across plaques before balloon angioplasty, including the soluble form of the endothelial lectin-like oxidized LDL receptor. Additional biomolecules, including matrix metallop ...[more]

PMID: 30062180

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Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.

Project description:BackgroundAs for the coronary artery inflammation and coronary atherosclerotic burden, which are used to assess the risk of adverse cardiac events in patients, it is unclear whether there is any certain correlation between them. Therefore, the purpose of this study was to explore the potential relationship between coronary artery inflammation and coronary atherosclerotic burden.MethodsA total of 346 eligible patients underwent assessment of computed tomography (CT) attenuation values of pericoronary adipose tissue (PCAT) in the right coronary artery and Agatston coronary artery calcium (CAC) based on coronary CT angiography. These measurements were utilized to evaluate coronary inflammation and atherosclerotic burden, respectively. Patients with a CAC score of 0 were categorized into groups based on the presence or absence of coronary artery disease (CAD). CAC scores of 10, 100, and 400 were chosen as cutoff values to compare differences in PCAT attenuation values across different CAC scores.ResultsWhen comparing all CAD patients to non-CAD patients, a significantly higher PCAT attenuation was observed in CAD patients (-87.54±9.39 vs. -93.45±7.42 HU, P=0.000). The PCAT attenuation in CAD patients with a CAC score of 0 was significantly higher than that in patients with a CAC score greater than 0 and in non-CAD patients with a CAC score of 0 (-82.63±8.70 vs. -90.38±8.59 vs. -93.45±7.42 HU, P=0.000). The PCAT attenuation values did not exhibit significant differences among different CAC scores (all P>0.05); however, it was highest in CAD patients with a CAC score of 0 (P<0.05). Body mass index, hyperlipidemia, hypertension, and PCAT attenuation were identified as independent risk factors in both CAD patients with a CAC score of 0 and patients with a CAC score greater than 0 (all P<0.05).ConclusionsThe results of this study suggest that a direct relationship between coronary inflammation and coronary atherosclerotic burden is not evident. Nonetheless, it is noteworthy that coronary inflammation was most pronounced in CAD patients with a CAC score of 0, while CAC score did not demonstrate an association with inflammation.

Dataset Information

Percutaneous Sampling of Local Biomolecule Gradients Across Coronary Artery Atherosclerotic Plaques.

Publications

Percutaneous Sampling of Local Biomolecule Gradients Across Coronary Artery Atherosclerotic Plaques.

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