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Am J Physiol Heart Circ Physiol 284: H644-H653, 2003; doi:10.1152/ajpheart.00494.2001
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Vol. 284, Issue 2, H644-H653, February 2003

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

Marjorie E. Zettler1, Michele A. Prociuk1, J. Alejandro Austria1, Hamid Massaeli1, Guangming Zhong2, and Grant N. Pierce1

1 Cell Biology Laboratory, Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, and the Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6; and 2 Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900

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.

atherosclerosis; cyclins; cyclin-dependent kinases; low-density lipoproteins


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