INVOLVEMENT OF LDL RECEPTOR IN THE PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS

To study the involvement of the low-density lipoprotein (LDL) receptor in the growth of vascular smooth muscle cells (VSMC), we compared the proliferation of cultured VSMC from Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack the LDL receptor, and VSMC from normal Jap anese white rabbits in response to platelet derived growth factor (PDG F), The increase in the number of VSMC from WHHL rabbits in response t o PDGF (10(-8) M) was significantly lower than that of VSMC from norma l rabbits. PDGF stimulated the synthesis of DNA in VSMC from both norm al rabbits and WHHL rabbits, but the response was significantly lower in the latter. To determine the involvement of the LDL receptor in the decreased mitogenic response of WHHL rabbit VSMC, we used an anti-LDL receptor monoclonal antibody (MAb) to normal rabbit VSMC; DNA synthes is of VSMC was stimulated by PDGF, but the effect was significantly bl ocked by the anti-LDL receptor MAb. Mitogen-activated protein (MAP) ki nase activity in normal rabbit VSMC was increased by exposure to PDGF, but the effect was significantly suppressed in the presence of the MA b. The anti-LDL receptor MAb markedly inhibited LDL binding to the sur face of normal rabbit VSMC. These results suggest that the LDL recepto r influences the proliferation of VSMC and thus might be involved in t he pathogenesis of atherosclerosis.