Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation

Marc S. Penn, Mei Zhen Cui, Allison L. Winokur, John Bethea, Thomas A. Hamilton, Paul E. DiCorleto, Guy M. Chisolm

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Tissue factor, which is expressed in vascular lesions, increases thrombin production, blood coagulation, and smooth muscle cell proliferation. We demonstrate that oxidized low-density lipoprotein (LDL) induces surface tissue factor pathway activity (ie, activity of the tissue factor: factor Vlla complex) on human and rat smooth muscle cells. Tissue factor messenger RNA (mRNA) was induced by oxidized LDL or native LDL; however, native LDL did not markedly increase tissue factor activity. We hypothesized that oxidized LDL mediated the activation of the tissue factor pathway via an oxidant-dependent mechanism, because antioxidants blocked the enhanced tissue factor pathway activity by oxidized LDL, but not the increased mRNA or protein induction. We separated total lipid extracts of oxidized LDL using high-performance liquid chromatography (HPLC). This yielded 2 major peaks that induced tissue factor activity. Of the known oxysterols contained in the first peak, 7α- or 7β-hydroxy or 7-ketocholesterol had no effect on tissue factor pathway activity; however, 7β-hydroperoxycholesterol increased tissue factor pathway activity without induction of tissue factor mRNA. Tertiary butyl hydroperoxide also increased tissue factor pathway activity, suggesting that lipid hydroperoxides, some of which exist in atherosclerotic lesions, activate the tissue factor pathway. We speculate that thrombin production could be elevated via a mechanism involving peroxidation of cellular lipids, contributing to arterial thrombosis after plaque rupture. Our data suggest a mechanism by which antioxidants may offer a clinical benefit in acute coronary syndrome and restenosis. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)3056-3063
Number of pages8
JournalBlood
Volume96
Issue number9
StatePublished - Nov 1 2000

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Thromboplastin
Lipid Peroxidation
Smooth Muscle Myocytes
Muscle
Chemical activation
Cells
Lipids
LDL Lipoproteins
Thrombin
oxidized low density lipoprotein
Messenger RNA
Antioxidants
Coronary Restenosis
Lipid Peroxides
Cell proliferation
High performance liquid chromatography
Blood Coagulation
Acute Coronary Syndrome
Coagulation
Oxidants

ASJC Scopus subject areas

  • Hematology

Cite this

Penn, M. S., Cui, M. Z., Winokur, A. L., Bethea, J., Hamilton, T. A., DiCorleto, P. E., & Chisolm, G. M. (2000). Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation. Blood, 96(9), 3056-3063.

Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation. / Penn, Marc S.; Cui, Mei Zhen; Winokur, Allison L.; Bethea, John; Hamilton, Thomas A.; DiCorleto, Paul E.; Chisolm, Guy M.

In: Blood, Vol. 96, No. 9, 01.11.2000, p. 3056-3063.

Research output: Contribution to journalArticle

Penn, MS, Cui, MZ, Winokur, AL, Bethea, J, Hamilton, TA, DiCorleto, PE & Chisolm, GM 2000, 'Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation', Blood, vol. 96, no. 9, pp. 3056-3063.
Penn MS, Cui MZ, Winokur AL, Bethea J, Hamilton TA, DiCorleto PE et al. Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation. Blood. 2000 Nov 1;96(9):3056-3063.
Penn, Marc S. ; Cui, Mei Zhen ; Winokur, Allison L. ; Bethea, John ; Hamilton, Thomas A. ; DiCorleto, Paul E. ; Chisolm, Guy M. / Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation. In: Blood. 2000 ; Vol. 96, No. 9. pp. 3056-3063.
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