GROWTH-STIMULATING EFFECT OF LIPOPROTEINS ON HUMAN ARTERIAL SMOOTH-MUSCLE CELLS AND LUNG FIBROBLASTS IS DUE TO APO-B-CONTAINING LIPOPROTEINS, TYPE LDL AND VLDL, AND REQUIRES LDL RECEPTORS

Excessive growth of the arterial smooth muscle is essential for the development of atherosclerosis and leads to arterial insufficiency in several other conditions. It is therefore important to elucidate the mechanisms that regulate the growth of the human arterial smooth-muscle cell, SMC. Like other untransformed cells, SMC require plasma for sustained growth in vitro. As found in an earlier study most of the material in plasma which stimulates SMC growth is related to the lipoproteins (LP), and is widespread among LP of different density classes. In the present study we investigated whether the growth stimulating activity might be more specifically related to certain lipoproteins defined by criteria other than density or particle size. Activity was assayed using human SMC and human lung fibroblasts as both a change of culture size and DNA synthesis. The growth-stimulating activity was confined to apo B-containing LP, as defined by their strong affinity to heparin-Sepharose, electrophoretic beta-mobility, the presence of apo B and the absolute requirement of low density lipoprotein (LDL) receptors for the growth-stimulating effect to appear. It was strongly potentiated by PDGF-BB. A much higher level of LDL was required to initiate synthesis of DNA in SMC than in fibroblasts but at optimal LDL concentration the degree of activation was similar for both cell types, Apo B-containing LP are very powerfully related to atherosclerosis. As intimal thickening is a primary change in atherogenesis, the growth-stimulating effect of them may be of direct pathogenetic importance.