HIGH-DENSITY-LIPOPROTEIN REDUCES EPIDERMAL GROWTH FACTOR-INDUCED DNA-SYNTHESIS IN VASCULAR SMOOTH-MUSCLE CELLS

High concentrations of high-density lipoprotein (HDL) are known to decrease the risk of coronary artery disease. In order to study the underlying cellular mechanisms, the influence of HDL on the epidermal growth factor (EGF)-induced vascular smooth muscle cell (VSMC) proliferation was investigated. Approximately 40% of the EGF-induced increase of the cell DNA synthesis was abolished in the presence of 30 mug/ml HDL. The EGF-induced dose-dependent (10 pg/ml to 100 ng/ml) increase in DNA synthesis was blunted by 30 mug/ml HDL. In addition HDL (3-300 mug/ml) caused a dose-dependent inhibition of EGF (20 ng/ml) -induced DNA synthesis, yielding a half maximal effective dose (ED50) of 30 mug/ml. Similar experiments with the HDL-protein and HDL-lipid fraction indicated that the HDL-protein fraction is most probably responsible for the observed inhibiting effects of HDL. This was confirmed by using purified apolipoprotein (apo) A-I and apo A-II. Both induced an approximately 800/o inhibition of the EGF-induced DNA synthesis. These results may help to explain the observed beneficial effects of HDL on cardiovascular diseases that are described in many epidemiological studies.