Blog
About

1
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Elastic Lamina Defects Are an Early Feature of Aortic Lesions in the Apolipoprotein E Knockout Mouse

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The aortae from male apolipoprotein E knockout (apoE–/–) mice were examined by serial section immunohistochemistry and electron microscopy to determine the continuity of the internal elastic lamina (IEL) and its association with developing intimal lesions. While in this model, defects in the elastic laminae have previously been described beneath advanced xanthomatous lesions, this study demonstrates that disruption of the IEL may be a primary factor in the localization and pathogenesis of intimal lesions in the apoE–/– mouse. IEL defects were found beneath early lesions in animals as young as 8 weeks of age. Small defects without associated intimal alteration were also observed. The elastic tissue defects beneath early intimal lesions were usually transversely orientated with abrupt ‘break’ edges. Regions consistent with direct enzymatic digestion of the IEL were relatively rare and only observed beneath advanced plaques, particularly in the brachiocephalic artery. The presence of IEL defects around branch sites of old C57BL/6J control mice along with their matching localization and morphology in apoE–/– appears consistent with biomechanical fatigue rather than direct enzymatic degradation. In conclusion, disruption of the IEL appears to be a prominent early, if not initial, feature of the apoE–/– model of atherosclerosis and may act as the nidus upon which intimal lesions develop.

          Related collections

          Most cited references 14

          • Record: found
          • Abstract: found
          • Article: not found

          Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse.

          The rupture of an atherosclerotic plaque is the main underlying cause of coronary artery thrombotic occlusion and subsequent myocardial infarction, but research into the causes and treatment of plaque rupture is hampered by the lack of a suitable animal model. Although complex atherosclerotic plaques can be induced in a number of experimental animal systems, in none of these is plaque rupture an established feature. We have surveyed branch points in the carotid arteries and aortas of apolipoprotein E knockout mice fed a diet supplemented with 21% lard and 0.15% cholesterol for up to 14 months. Six male and five female mice were used. Four of the male mice and four of the female mice died, after 46+/-3 weeks of feeding (range 37-59 weeks). Lumenal thrombus associated with atherosclerotic plaque rupture was observed in three male and all four female mice. In six of these seven mice, an atherosclerotic plaque rupture was found where the brachiocephalic artery branches into the right common carotid and right subclavian arteries. The ruptures were characterised by fragmentation and loss of elastin in the fibrous caps of relatively small and lipid-rich plaques overlying large complex lesions, with intraplaque haemorrhage. Immunocytochemical analysis revealed loss of smooth muscle cells from ruptured caps. These data suggest that long-term fat-feeding of apolipoprotein E knockout mice is a useful and reproducible model of atherosclerotic plaque rupture, and that these ruptures occur predominantly in the brachiocephalic artery.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption.

             B Burkey,  N Maeda,  R Reddick (1994)
            With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet. The other six normals had no lesions. Our study demonstrates that heterozygous mice with only one functional apo E gene are more susceptible to diet-induced atherosclerosis than are normal, two-copy mice. Genetically determined quantitative limitations of apo E could, therefore, have similar effects in humans when they are stressed by an atherogenic diet.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Apolipoprotein E and atherosclerosis.

              Apolipoprotein E plays a key protective role in atherosclerosis. Its capacity to safeguard against this disease can be attributed to at least three distinct functions. First, plasma apolipoprotein E maintains overall plasma cholesterol homeostasis by facilitating efficient hepatic uptake of lipoprotein remnants. Second, lesion apolipoprotein E in concert with apolipoprotein A-I facilitates cellular cholesterol efflux from macrophage foam cells within the intima of the lesion. Third, lesion apolipoprotein E directly modifies both macrophage- and T lymphocyte-mediated immune responses that contribute to this chronic inflammatory disease.
                Bookmark

                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2005
                June 2005
                03 June 2005
                : 42
                : 3
                : 237-246
                Affiliations
                Departments of aSurgery and bBiochemistry, Otago Medical School, Dunedin, New Zealand, and cHoward Florey Institute, University of Melbourne, Parkville, Australia
                Article
                85553 J Vasc Res 2005;42:237–246
                10.1159/000085553
                15860923
                © 2005 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.

                Page count
                Figures: 8, References: 30, Pages: 10
                Categories
                Research Paper

                Comments

                Comment on this article