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Research ArticleCARDIOVASCULAR

Statins Modulate Oxidized Low-Density Lipoprotein-Mediated Adhesion Molecule Expression in Human Coronary Artery Endothelial Cells: Role of LOX-1

Dayuan Li, Hongjiang Chen, Francesco Romeo, Tatsuya Sawamura, Tom Saldeen and Jawahar L. Mehta
Journal of Pharmacology and Experimental Therapeutics August 2002, 302 (2) 601-605; DOI: https://doi.org/10.1124/jpet.102.034959
Dayuan Li
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Hongjiang Chen
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Francesco Romeo
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Tatsuya Sawamura
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Tom Saldeen
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Jawahar L. Mehta
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Abstract

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis. LOX-1 activation also plays an important role in monocyte adhesion to endothelial cells. A number of studies show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce total LDL cholesterol and exert a cardioprotective effect. We examined the modulation of LOX-1 expression and its function by two different statins, simvastatin and atorvastatin, in human coronary artery endothelial cells (HCAECs). We observed that ox-LDL (40 μg/ml) treatment up-regulated the expression of E- and P-selectins, VCAM-1 and ICAM-1 in HCAECs. Ox-LDL mediated these effects via LOX-1, since antisense to LOX-1 mRNA decreased LOX-1 expression and subsequent adhesion molecule expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 μM) reduced ox-LDL-induced expression of LOX-1 as well as adhesion molecules (all P < 0.05). A high concentration of statins (10 μM) was more potent than the low concentration (1 μM) (P < 0.05). Both statins reduced ox-LDL-mediated activation of the redox-sensitive nuclear factor-κB (NF-κB) but not AP-1. These observations indicate that LOX-1 activation plays an important role in ox-LDL-induced expression of adhesion molecules. Inhibition of expression of LOX-1 and adhesion molecules and activation of NF-κB may be another mechanism of beneficial effects of statins in vascular diseases.

Footnotes

  • Supported by Scientist Development Grant and Beginning grant-in-aid from the American Heart Association, a Merit Review Award from the Veterans Affairs Central Office, and a contract with the Department of Defense.

  • DOI: 10.1124/jpet.102.034959

  • Abbreviations:
    ox-LDL
    oxidized low-density lipoprotein
    eNOS
    endothelial nitric-oxide synthase
    AP-1
    activating protein-1
    VCAM-1
    vascular cell adhesion molecule-1
    ICAM-1
    intercellular adhesion molecule-1
    NF-κB
    nuclear factor-κB
    HCAECs
    human coronary artery endothelial cells
    PCR
    polymerase chain reaction
    • Received February 18, 2002.
    • Accepted March 27, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 302 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 302, Issue 2
1 Aug 2002
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Research ArticleCARDIOVASCULAR

Statins Modulate Oxidized Low-Density Lipoprotein-Mediated Adhesion Molecule Expression in Human Coronary Artery Endothelial Cells: Role of LOX-1

Dayuan Li, Hongjiang Chen, Francesco Romeo, Tatsuya Sawamura, Tom Saldeen and Jawahar L. Mehta
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 601-605; DOI: https://doi.org/10.1124/jpet.102.034959

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Research ArticleCARDIOVASCULAR

Statins Modulate Oxidized Low-Density Lipoprotein-Mediated Adhesion Molecule Expression in Human Coronary Artery Endothelial Cells: Role of LOX-1

Dayuan Li, Hongjiang Chen, Francesco Romeo, Tatsuya Sawamura, Tom Saldeen and Jawahar L. Mehta
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 601-605; DOI: https://doi.org/10.1124/jpet.102.034959
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