Modified low density lipoprotein is a potent stimulus for smooth muscle cell outgrowth from rat aortic explant in vitro

Abstract

Outgrowth of vascular wall cells from rat aortic tissue explant was studied. In addition to fresh rat serum (3%), the complete culture medium contained either low density lipoprotein (LDL) separated from rat plasma (n-LDL, 100 μg/ml) or rat LDL modified either by activated rat polymorphonuclear leucocytes (pmn-LDL) or by exposure to UV light (uv-LDL). Compared to n-LDL, pmn-LDL significantly increased the start of cell outgrowth and the further rate of growth. High concentration of uv-LDL (500 μg/ml) was cytotoxic. Cells which grew out from aortic tissue in the presence of n-LDL were characterised as endothelial cells by staining with lectin Ulex europaeus, with monoclonal antibody to Factor VIII or with monoclonal antibody to endothelial cells (CD31). However, cells which grew out in the presence either of pmn-LDL or uv-LDL did not stain with any of these endothelial cell markers, instead they showed intense staining with monoclonal anti- α-smooth muscle actin, indicating that they were smooth muscle cells. Growth rate of subcultured rat aortic smooth muscles cells was increased ( P<0.05) by the presence of uv-LDL (100 μg/ml). It is concluded that LDL modified either by activated leucocytes or by UV light prevents the normal outgrowth of endothelial cells from aortic explant and at the same time greatly promotes outgrowth of smooth muscle cells. Stimulation of both outgrowth of smooth muscle cells from vascular tissue and their proliferation by modified (oxidised) LDL may have important pathological significance in atherogenesis and restenosis.