ATYPICAL LOW-DENSITY-LIPOPROTEIN BINDING-SITE THAT MAY MEDIATE LIPOPROTEIN-INDUCED SIGNAL-TRANSDUCTION

The characteristics of low density lipoprotein (LDL) binding in quiesc ent cultures of human vascular smooth muscle cells (VSMC) have been fu rther investigated and compared with the characteristics of high affin ity LDL binding in human fibroblasts [via the apolipoprotein (ape) B/E receptor] and with the properties of LDL-induced phosphoinositide cat abolism in VSMC. In VSMC the bulk of specific I-125-LDL binding occurs at a low affinity site, several characteristics of which are distinct from those of I-125-LDL binding to the apo B/E receptor in fibroblast s. (a) The affinity of LDL binding in VSMC is 25-50 times lower than t hat in fibroblasts (K-d approximate to 50 mu g/ml versus K-d approxima te to 2 mu g/ml). (b) The kinetics of LDL association and dissociation in VSMC are more rapid than those in fibroblasts. (c) In contrast to apo B/E receptor-mediated binding of LDL in fibroblasts, binding of LD L to VSMC is insensitive to heparin, chemical modification of lysine r esidues, and chelation (with EDTA) of divalent cations. (d) Apo E-free high density lipoprotein(3) displaces labeled LDL more effectively in VSMC than in fibroblasts. (e) The ratio of bound/internalized LDL to degraded LDL differs markedly between fibroblasts and VSMC. LDL-stimul ated phosphoinositide catabolism in VSMC, which occurs with an activat ion constant similar to the K-d for low affinity LDL binding, is insen sitive to heparin, modification of lysine and arginine residues in LDL , and chelation of divalent cations. Thus, the atypical low affinity r eceptor in these cells may mediate the effects of LDL on signal transd uction.