Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCARDIOVASCULAR

Effect of Cyclosporine on HMG-CoA Reductase, Cholesterol 7α-Hydroxylase, LDL Receptor, HDL Receptor, VLDL Receptor, and Lipoprotein Lipase Expressions

Nosratola D. Vaziri, Kaihui Liang and Habib Azad
Journal of Pharmacology and Experimental Therapeutics August 2000, 294 (2) 778-783;
Nosratola D. Vaziri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaihui Liang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Habib Azad
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Long-term administration of cyclosporine (CsA) has been shown to cause hypercholesteremia, hypertriglyceridemia, and elevations of plasma low-density and very low-density lipoprotein (LDL and VLDL) levels in humans. This study was undertaken to explore the effects of CsA on expressions of the key lipid regulatory enzymes and receptors. Thus, hepatic expressions of cholesterol 7α-hydroxylase (the rate-limiting step in cholesterol conversion to bile acids), LDL receptor, and high-density lipoprotein (HDL) receptor proteins, as well as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were determined in rats treated with CsA (18 mg/kg/day) or placebo for 3 weeks. In addition, skeletal muscle and adipose tissue expressions of lipoprotein lipase and VLDL receptor were measured. Western blot analysis was used for all protein measurements using appropriate antibodies against the respective proteins. CsA-treated animals showed mild but significant elevations of plasma cholesterol and triglyceride concentrations. This was associated with a marked down-regulation of cholesterol 7α-hydroxylase in the liver and a severe reduction of lipoprotein lipase abundance in skeletal muscle and adipose tissue. However, hepatic LDL receptor and HDL receptor expressions and HMG-CoA reductase activity were not altered by CsA therapy. Likewise, skeletal muscle and adipose tissue VLDL receptor protein expressions were unaffected by CsA administration under the given condition. In conclusion, CsA administration for 3 weeks resulted in a significant reduction of hepatic cholesterol 7α-hydroxylase and marked down-regulation of skeletal muscle and adipose tissue lipoprotein lipase abundance in rats. The former abnormality can contribute to hypercholesterolemia by limiting cholesterol catabolism, whereas the latter may contribute to hypertriglyceridemia and VLDL accumulation by limiting triglyceride-rich lipoprotein clearance in CsA-treated animals.

Footnotes

  • Send reprint requests to: Dr. N. D. Vaziri, M.D., MACP, University of California Irvine Medical Center, 101 The City Drive, Orange, CA 92668. E-mail: ndvaziri{at}uci.edu

  • ↵1 This study was generously supported by Mr. and Mrs. William Chou.

  • Abbreviations:
    CsA
    cyclosporine
    HDL
    high-density lipoprotein
    HMG-CoA
    3-hydroxy-3-methylglutaryl coenzyme A
    IDL
    intermediate-density lipoprotein
    LDL
    low-density lipoprotein
    VLDL
    very low-density lipoprotein
    • Received January 21, 2000.
    • Accepted May 8, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 294 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 2
1 Aug 2000
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Effect of Cyclosporine on HMG-CoA Reductase, Cholesterol 7α-Hydroxylase, LDL Receptor, HDL Receptor, VLDL Receptor, and Lipoprotein Lipase Expressions
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCARDIOVASCULAR

Effect of Cyclosporine on HMG-CoA Reductase, Cholesterol 7α-Hydroxylase, LDL Receptor, HDL Receptor, VLDL Receptor, and Lipoprotein Lipase Expressions

Nosratola D. Vaziri, Kaihui Liang and Habib Azad
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 778-783;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleCARDIOVASCULAR

Effect of Cyclosporine on HMG-CoA Reductase, Cholesterol 7α-Hydroxylase, LDL Receptor, HDL Receptor, VLDL Receptor, and Lipoprotein Lipase Expressions

Nosratola D. Vaziri, Kaihui Liang and Habib Azad
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 778-783;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • 4-Chloro ring-substituted synthetic cathinones
  • 14-3-3 Influences Nav1.5 Response to Anti-Arrhythmic Drugs
  • Inhaled Treprostinil Palmitil in the Sugen/Hypoxia Rat Model
Show more Cardiovascular

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics