Oxidized low-density lipoprotein induces cytoskeletal disorganization in smooth muscle cells

Vascular smooth muscle cells in atherosclerotic vessels proliferate and cha nge from a contractile to a synthetic phenotype. To determine whether oxidi zed 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 oxLD L employed. Confocal microscopic images of cells immunostained for smooth m uscle-specific alpha-actin and myosin showed a normal, elongated alignment of myofilaments in cells after incubation with native LDL. Surprisingly, wh en the cells were treated with oxLDL, actin and myosin filaments underwent a striking process of disorganization and accumulation into ball-shaped agg regates. These changes were dependent on the duration and concentration of oxLDL employed. Our results demonstrate that oxLDL has the capacity to decr ease the content of myofilaments in smooth muscle cells. The loss in myosin and actin protein may be associated with an unusual formation of large cel lular aggregates that appear to be in the process of being expelled from th e cell.