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      Downregulations of CD36 and Calpain-1, Inflammation, and Atherosclerosis by Simvastatin in Apolipoprotein E Knockout Mice

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          Abstract

          Background: In the previous in vitro study, we found that simvastatin decreased the protein expression of CD36, the scavenger receptor, and calpain-1, the Ca<sup>2+</sup>-sensitive cysteine protease, in oxidized low-density lipoprotein (oxLDL)-treated macrophages. In this in vivo study, we investigated whether simvastatin downregulates the expression of CD36 and calpain-1 and inhibits the inflammation and atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. Methods: Twenty male 6-week-old ApoE KO mice were divided into 2 groups: the ApoE KO group and the ApoE KO + simvastatin (ApoE KO + Sim) group. Atherosclerotic lesions were evaluated and the expressions of CD68, CD36, and calpain-1 in aorta were examined. Results: Simvastatin inhibited the atherosclerotic lesion in ApoE KO mice. In addition, simvastatin reduced the contents of oxLDL, thiobarbituric acid reactive substances, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum, decreased the mRNA and protein expressions of CD36 and reduced the mRNA expression of TNF-α and IL-6 in the aortas. Furthermore, simvastatin reduced the calpain activity and the protein expression of calpain-1 in the aorta. Conclusion: The results suggested that the attenuation of atherosclerotic lesions in ApoE KO mice by simvastatin might be associated with the downregulations of CD36 and calpain-1 and with inflammation.

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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
          2017
          May 2017
          28 April 2017
          : 54
          : 3
          : 123-130
          Affiliations
          aKey Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, and bInternal Medicine-Cardiovascular Departments, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, cCentral Hospital of Yingkou Development Areas, Yingkou, and dGuangdong Metabolic Diseases Research Center, Guangdong Pharmaceutical University, Guangzhou, China
          Author notes
          *Dr. Futian Tang, Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001 (China), E-Mail tangft@163.com, Dr. Jiao Guo, Guangdong Metabolic Diseases Research Center, Guangdong Pharmaceutical University, No. 280, Waihuan East Road, Guangzhou 510006 (China), E-Mail Guoj@gdpu.edu.cn
          Article
          464288 J Vasc Res 2017;54:123-130
          10.1159/000464288
          28448973
          ddd9a37f-4d2e-46a3-a7e1-9c3fa1aa34a3
          © 2017 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.

          History
          : 12 December 2016
          : 18 February 2017
          Page count
          Figures: 5, References: 31, Pages: 8
          Categories
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          CD36,Inflammation,Simvastatin,Atherosclerosis,Apolipoprotein E knockout,Calpain-1

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