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      Circulating Autoantibodies to Oxidized Low-Density Lipoprotein in Patients with Ascending Aortic Aneurysms: Marker of Oxidative Stress Involved in Pathogenesis, Epiphenomenon of Endothelial Dysfunction, or Pure Chance?

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          Most cited references 13

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          Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms.

          The role of inflammation in the pathogenesis of abdominal aortic aneurysms (AAA) is well established. The inflammatory process leads to protease-mediated degradation of the extracellular matrix and apoptosis of smooth muscle cells (SMC), which are the predominant matrix synthesizing cells of the vascular wall. These processes act in concert to progressively weaken the aortic wall, resulting in dilatation and aneurysm formation. Oxidative stress is invariably increased in, and contributes importantly to, the pathophysiology of inflammation. Moreover, reactive oxygen species (ROS) play a key role in regulation of matrix metalloproteinases and induction of SMC apoptosis. ROS may also contribute to the pathogenesis of hypertension, a risk factor for AAA. Emerging evidence suggests that ROS and reactive nitrogen species (RNS) are associated with AAA formation in animal models and in humans. Although experimental data are limited, several studies suggest that modulation of ROS production or activity may suppress AAA formation and improve experimental outcome in rodent models. Although a number of enzymes can produce injurious ROS in the vasculature, increasing evidence points toward a role for NADPH oxidase as a source of oxidative stress in the pathogenesis of AAA.
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            Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events.

            The relationship between autoantibodies to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL autoantibodies to malondialdehyde (MDA)-modified LDL, copper oxidized low density lipoprotein (CuOxLDL), and oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (apoB-ICs), were measured in 504 patients undergoing clinically indicated coronary angiography. Patients were followed for cardiovascular events for a median of 4 years. In univariate analysis, IgM OxLDL autoantibodies and IgM apoB-ICs were inversely associated with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated. In logistic regression analysis, compared with the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and apoB-ICs showed a lower probability of angiographically determined CAD (>50% diameter stenosis). Odds ratios and (95% confidence intervals) were as follows: MDA-LDL, 0.51 (0.32-0.82; P = 0.005); CuOxLDL, 0.63 (0.39-1.01; P = 0.05); OxCL, 0.63 (0.39-1.01; P = 0.05); and apoB-IC, 0.55 (0.34-0.88; P = 0.013). These relationships were accentuated in the setting of hypercholesterolemia, with the highest IgM levels showing the lowest risk of CAD for the same level of hypercholesterolemia. Multivariable analysis revealed that neither IgM or IgG OxLDL autoantibodies nor apoB-ICs were independently associated with angiographically determined CAD or cardiovascular events. In conclusion, IgG and IgM OxLDL biomarkers have divergent associations with CAD in univariate analysis but are not independent predictors of CAD or clinical events.
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              Evaluation of 3D blood flow patterns and wall shear stress in the normal and dilated thoracic aorta using flow-sensitive 4D CMR

              Background The purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers. Methods Thoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified. Results Incidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, P<.05) or healthy volunteers (1/15 and 0/15, grade 0.1 ± 0.3 P<.05). Greater strength of the ascending aortic helix and vortex flow were associated with significant differences in AAo diameters (P<.05). Peak systolic WSS in the ascending aorta and aortic arch was significantly lower in patients with dilated AAo (P<.0157-.0488). AAo diameter positively correlated to time to peak systolic velocities (r=0.30-0.53, P<.04), OSI (r=0.33-0.49, P<0.02) and inversely correlated to peak systolic WSS (r=0.32-0.40, P<.03). Peak systolic WSS was significantly lower in AAo aneurysms at the right and outer curvature within the AAo and proximal arch (P<.01-.05). Conclusions Increase in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2014
                May 2014
                22 March 2014
                : 128
                : 2
                : 92-94
                Affiliations
                Faculty of Medicine, University of Athens, and Department of Cardiac Surgery, Attikon University Hospital, Athens, Greece
                Author notes
                *Dimitrios C. Angouras, MD, Department of Cardiac Surgery, Attikon University Hospital, 1 Rimini Street, Chaidari, GR-12462 Athens (Greece), E-Mail dangouras@yahoo.com
                Article
                358726 Cardiology 2014;128:92-94
                10.1159/000358726
                24662773
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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