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      Low-Dose Cerivastatin Inhibits Spontaneous Atherogenesis in Heterozygous Watanabe Hyper lipidemic Rabbits

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          Abstract

          The aim of this study was to investigate whether cerivastatin (BAYw6228), a new potent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, was able to prevent atherogenesis in heterozygous Watanabe heritable-hyperlipidemic (WHHL) rabbits, a model never tested before using this HMG-CoA reductase inhibitor. The heterozygous WHHL rabbits of our breeding developed mild hypercholesterolemia along with focal atherosclerotic lesions in the thoracic aorta. A 9-week treatment with cerivastatin at doses comparable to those used in humans (50 μg/kg/day) reduced serum total cholesterol levels (from 94.4 ± 10.9 to 43.6 ± 10.5 mg/dl, p < 0.005) and prevented aortic lesion development (intima/media ratio: 0.058 ± 0.032 vs 0.946 ± 0.282 in the placebo group, p < 0.0005). Using a panel of monoclonal antibodies specific to macrophages and able to recognize different smooth muscle cell (SMC) phenotypes, we observed that cerivastatin treatment affected the differentiation properties of SMCs and drastically reduced SMC and macrophage accumulation in the intima of the thoracic aorta. These data show that in the presence of moderate atherosclerotic lesions, such as those of heterozygous WHHL rabbits, low doses of cerivastatin exert an antiatherogenic effect.

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          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
          2000
          June 2000
          24 May 2000
          : 37
          : 3
          : 189-194
          Affiliations
          aDipartimento di Medicina Clinica e Sperimentale e bDipartimento di Scienze Biomediche, Università di Padova, Padova, Italy
          Article
          25730 J Vasc Res 2000;37:189–194
          10.1159/000025730
          10859477
          © 2000 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: 2, References: 15, Pages: 6
          Categories
          Research Paper

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