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Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, and Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6
Vascular smooth muscle cells in
atherosclerotic vessels proliferate and change from a contractile to a
synthetic phenotype. To determine whether oxidized low-density
lipoprotein (oxLDL) is involved in this transformation, we chronically
incubated cultured smooth muscle cells with native and oxidized LDL.
Western blot analysis detected a decrease in actin and myosin content
in treated cells. This was dependent on the time and concentration of
oxLDL employed. Confocal microscopic images of cells immunostained for smooth muscle-specific
-actin and myosin showed a normal, elongated alignment of myofilaments in cells after incubation with native LDL.
Surprisingly, when the cells were treated with oxLDL, actin and myosin
filaments underwent a striking process of disorganization and
accumulation into ball-shaped aggregates. These changes were dependent
on the duration and concentration of oxLDL employed. Our results
demonstrate that oxLDL has the capacity to decrease the content of
myofilaments in smooth muscle cells. The loss in myosin and actin
protein may be associated with an unusual formation of large cellular
aggregates that appear to be in the process of being expelled from the cell.
atherosclerosis; smooth muscle; cytoskeleton; contractile proteins; actin; myosin
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