OxLDL stimulates cell proliferation through a general induction of cell cycle proteins

Marjorie E. Zettler, Michele A. Prociuk, J. Alejandro Austria, Hamid Massaeli, Guangming Zhong, Grant N. Pierce

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Oxidized low-density lipoprotein (oxLDL) may be involved in atherosclerosis by stimulating proliferation of cells in the vessel wall. The purpose of this study was to identify the mechanism by which oxLDL induces proliferation. Quiescent human fibroblasts and rabbit smooth muscle cells were treated with 0, 10, or 50 μg/ml oxLDL for 24-48 h. This resulted in significant increases in total cell counts at both concentrations of oxLDL, at both time points, for both types of cells. Western blot analysis revealed that oxLDL-stimulated cell proliferation was associated with significant increases in the expression of proteins that regulate entry into and progression through the cell cycle [cell division cycle 2, cyclin-dependent kinase (cdk) 2, cdk 4, cyclin B1, cyclin D1, and PCNA]. Surprisingly, the expression of cell cycle inhibitors (p21 and p27) was stimulated by oxLDL as well, but this was to a lesser extent than the effects on cell cycle-activating proteins. OxLDL also induced nuclear localization of all cell cycle proteins examined. The similar effects of oxLDL on the translocation and expression of both cell cycle-activating and -inhibiting proteins may explain the controlled proliferative phenomenon observed in atherosclerosis as opposed to the more rapid proliferative event characteristic of cancer.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number2 53-2
Publication statusPublished - 1 Feb 2003
Externally publishedYes

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Cell Cycle Proteins
Cell Proliferation
Cell Cycle
Atherosclerosis
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 2
Cyclin B1
oxidized low density lipoprotein
Cyclin D1
Proliferating Cell Nuclear Antigen
Smooth Muscle Myocytes
Proteins
Fibroblasts
Cell Count
Western Blotting
Rabbits

Keywords

  • Atherosclerosis
  • Cyclin-dependent kinases
  • Cyclins
  • Low-density lipoproteins

ASJC Scopus subject areas

  • Physiology

Cite this

OxLDL stimulates cell proliferation through a general induction of cell cycle proteins. / Zettler, Marjorie E.; Prociuk, Michele A.; Austria, J. Alejandro; Massaeli, Hamid; Zhong, Guangming; Pierce, Grant N.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 2 53-2, 01.02.2003.

Research output: Contribution to journalArticle

Zettler, Marjorie E. ; Prociuk, Michele A. ; Austria, J. Alejandro ; Massaeli, Hamid ; Zhong, Guangming ; Pierce, Grant N. / OxLDL stimulates cell proliferation through a general induction of cell cycle proteins. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 284, No. 2 53-2.
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