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Elevated Levels of Circulating DNA and Chromatin Are Independently Associated With Severe Coronary Atherosclerosis and a Prothrombotic State

Published on Aug 1, 2013in Arteriosclerosis, Thrombosis, and Vascular Biology6.618
· DOI :10.1161/ATVBAHA.113.301627
Julian I. Borissoff11
Estimated H-index: 11
,
Ivo A. Joosen11
Estimated H-index: 11
+ 10 AuthorsBas L.J.H. Kietselaer14
Estimated H-index: 14
Abstract
Objective—Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps. This extracellular DNA exerts potent proinflammatory, prothrombotic, and cytotoxic properties. The goal of this study was to examine the relationships among extracellular DNA formation, coronary atherosclerosis, and the presence of a prothrombotic state. Approach and Results—In a prospective, observational, cross-sectional cohort of 282 individuals with suspected coronary artery disease, we examined the severity, extent, and phenotype of coronary atherosclerosis using coronary computed tomographic angiography. Double-stranded DNA, nucleosomes, citrullinated histone H4, and myeloperoxidase–DNA complexes, considered in vivo markers of cell death and NETosis, respectively, were established. We further measured various plasma markers of coagulation activation and inflammation. Plasma double-stranded DNA, nucleosomes, and myeloperoxidase–DNA complexes were positively associated with thrombin generation and significantly elevated in patients with severe coronary atherosclerosis or extremely calcified coronary arteries. Multinomial regression analysis, adjusted for confounding factors, identified high plasma nucleosome levels as an independent risk factor of severe coronary stenosis (odds ratio, 2.14; 95% confidence interval, 1.26–3.63; P=0.005). Markers of neutrophil extracellular traps, such as myeloperoxidase–DNA complexes, predicted the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events. Conclusions—Our report provides evidence demonstrating that markers of cell death and neutrophil extracellular trap formation are independently associated with coronary artery disease, prothrombotic state, and occurrence of adverse cardiac events. These biomarkers could potentially aid in the prediction of cardiovascular risk in patients with chest discomfort. (Arterioscler Thromb Vasc Biol. 2013;33:2032-2040.)
  • References (51)
  • Citations (153)
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References51
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#1Mathijs O. Versteylen (UM: Maastricht University)H-Index: 10
#2Bas L.J.H. Kietselaer (UM: Maastricht University)H-Index: 14
Last. Leonard Hofstra (UM: Maastricht University)H-Index: 26
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Objectives The purpose of this study was to investigate whether the use of a semiautomated plaque quantification algorithm (reporting volumetric and geometric plaque properties) provides additional prognostic value for the development of acute coronary syndromes (ACS) as compared with conventional reading from cardiac computed tomography angiography (CCTA). Background CCTA enables the visualization of coronary plaque characteristics, of which some have been shown to predict ACS. Methods A total ...
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#1Kimberly Martinod (Harvard University)H-Index: 21
#2Mélanie Demers (Harvard University)H-Index: 20
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Deep vein thrombosis and pulmonary embolism are major health problems associated with high mortality. Recently, DNA-based neutrophil extracellular traps (NETs) resulting from the release of decondensed chromatin, were found to be part of the thrombus scaffold and to promote coagulation. However, the significance of nuclear decondensation and NET generation in thrombosis is largely unknown. To address this, we adopted a stenosis model of deep vein thrombosis and analyzed venous thrombi in peptidy...
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#2Jeroen J. T. Otten (UM: Maastricht University)H-Index: 5
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