[Atypical binding sites of low density lipoproteins in human vascular smooth muscle cells]

Lipoprotein-binding sites on cultured human omental vascular smooth muscle cells have been investigated. Two sites specifically binding low density lipoprotein (Kd1 = 1 microgram/ml and Kd2 = 50 micrograms/ml) were found. The properties of the high affinity site are similar to those of the previously described "classical" apo B,E-receptor. The nature of the second site is not clear. Binding to this low affinity site is saturable at physiological concentrations of LDL, is reversible and demonstrates a significant selectivity for LDL as compared to HDL3. In contrast with the apo B,E-receptor, the interaction of LDL with the low affinity site is not heparin-sensitive, does not require the presence of bivalent cations and is not abolished after modification of lysine residues of apo B. The kinetic characteristics of the LDL interaction with the low affinity site are in good correlation with the parameters of activation of second messenger systems. The Kd2 value of LDL binding is close to the LDL concentration inducing a half-maximal elevation of inositol phosphates and cytoplasmic Ca2+ level. Acetylation or carbamylation of apo B does not influence the ability of LDL to activate cell-signalling systems. Also, LDL-induced activation of the phosphoinositide turnover is not sensitive to heparin and EDTA. The data obtained support the hypothesis that the low affinity LDL-binding site mediates lipoprotein-induced activation of second messenger systems in human vascular smooth muscle cells.