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Molecular Biology Reports

, Volume 39, Issue 6, pp 6857–6866 | Cite as

Alpha-lipoic acid attenuates atherosclerotic lesions and inhibits proliferation of vascular smooth muscle cells through targeting of the Ras/MEK/ERK signaling pathway

  • Woo-Ram Lee
  • Aekyong Kim
  • Kee-Sik Kim
  • Yoon-Yub Park
  • Ji-Hyun Park
  • Kyung-Hyun Kim
  • Soo-Jung Kim
  • Kwan-Kyu ParkEmail author
Article

Abstract

An infectious burden has been suggested to be associated with atherosclerosis in humans, based on the shared and underlying inflammatory responses during infection and atherosclerosis. However, the efficacy of anti-atherogenic drugs is yet to be tested against atherosclerosis in a scenario involving an infectious burden. We have examined alpha-lipoic acid (ALA) for anti-atherogenic effects in a hypercholesterolemic diet-induced atherosclerotic mouse model with inflammatory stimulation. C57BL/6 mice were fed with a hypercholesterolemic diet for 12 weeks to induce atherosclerosis. Lipopolysaccharide was intraperitoneally injected for the 1st week of study to simulate underlying infectious burden during development of atherosclerosis. ALA treatment alleviated atherosclerotic pathologies and reduced serum cholesterol and inflammatory cytokines. Consistently, atherosclerotic markers were improved by ALA treatment. In addition, ALA attenuated the proliferation and migration of vascular smooth muscle cells upon platelet-derived growth factor stimulation through the targeting of the Ras-MEK1/2-ERK1/2 pathway. This study demonstrates the efficacy of ALA on atherosclerosis with immunological complication, by showing that ALA modulates multiple pathogenic aspects of atherosclerosis induced by a hypercholesterolemic diet with inflammatory stimulation consisting of hypercholesterolemia, inflammation and VSMC activation.

Keywords

Alpha-lipoic acid Atherosclerosis VSMC Lipopolysaccharide 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Woo-Ram Lee
    • 1
  • Aekyong Kim
    • 2
  • Kee-Sik Kim
    • 3
  • Yoon-Yub Park
    • 4
  • Ji-Hyun Park
    • 1
  • Kyung-Hyun Kim
    • 1
  • Soo-Jung Kim
    • 1
  • Kwan-Kyu Park
    • 1
    Email author
  1. 1.Department of Pathology, College of MedicineCatholic University of DaeguDaeguSouth Korea
  2. 2.College of PharmacyCatholic University of DaeguDaeguSouth Korea
  3. 3.Department of Internal Medicine, College of MedicineCatholic University of DaeguDaeguSouth Korea
  4. 4.Department of Physiology, College of MedicineCatholic University of DaeguDaeguSouth Korea

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