ACTIVATION OF PHOSPHOINOSITIDE CATABOLISM AND DNA-SYNTHESIS IN VASCULAR SMOOTH-MUSCLE CELLS BY LDL AND POSITIVELY CHARGED PROTEINS - EVIDENCE THAT EFFECTS OF LDL ARE NOT SPECIFICALLY DEPENDENT ON THE POLYCATIONIC NATURE OF APO-B

We have investigated whether the polycationic structure of apo B is an important determinant for the recognition of low density lipoprotein (LDL) by putative signalling-coupled/growth receptor(s). Using culture s of human vascular smooth muscle cells (VSMC),the effects of LDL on p hosphoinositide (PI) catabolism and DNA synthesis have been compared w ith those of a variety of proteins which, like apo B, possess a strong positive charge. Using myo-[2-H-3]-inositol-prelabelled VSMC, the pol ycationic proteins protamine and histones II-S, III-S, V-S and VII-S, but not low-molecular weight polyamines (putrescine and spermine), wer e found to stimulate PI catabolism in a dose- and time-dependent manne r. In contrast to LDL which induced rapid, transient increases in inos itol tris- and bis-phosphates and a delayed sustained increase in inos itol monophosphate, the PI response of VSMC to polycationic proteins w as characterized by a potent, sustained increase in inositol bisphosph ate and the absence of an inositol trisphosphate transient. Heparin in hibited the PI catabolic response of VS MC to histones and protamine b ut was without effect on LDL-stimulated PI catabolism. Like LDL, polyc ationic proteins also stimulated DNA synthesis in VSMC (incorporation of [H-3]-thymidine). The data indicate that signalling/growth effects of LDL and positively charged protein occur via distinct mechanisms an d that the effects of LDL do not primarily depend upon the polycationi c properties of apo B. (C) 1994 Academic Press, Inc.