HORMONE-LIKE EFFECTS OF PLASMA-LIPOPROTEINS ON HUMAN PLATELETS AND VASCULAR SMOOTH-MUSCLE CELLS

The fluorescent Ca2+-sensitive probes Quin 2 and Fura 2 were used to s tudy plasma lipoprotein-induced transients of cytosolic calcium, [Ca2](4,)(i) in washed human platelets and cultured smooth muscle cells fr om human aorta. With both types of cells HDL(3) and LDL were shown to induce rapid and reversible increase in [Ca2+](i) levels. The effects were dose-dependent and attained saturation at physiological HDL(3) an d LDL in concentrations. The lipoproteins were also capable of stimula ting phosphoinositides turnover, with the resulting accumulation of DA G, IP1, IP2, and IP3. HPLC analysis of inositol phosphate isomers demo nstrated that LDL and HDL(3) activated the polyphosphoinositide-specif ic phospholipase C. These data were suggestive of lipoprotein similari ty to aggregation inducers and vasoactive hormones, which activate sec ond messenger systems in platelets and smooth muscle cells, respective ly. The hormone-like effects of lipoproteins on the cells were inhibit ed by protein kinase C activators, as well as by agents capable of sti mulating cAMP- and cGMP-dependent protein kinases. The lipoprotein-ind uced [Ca2+](i) elevation was significantly attenuated if the smooth mu scle cells were pretreated by Bordetella pertussis toxin. In contrast, LDL-induced [Ca2+](i) increase was 2 to 3 times more pronounced in th e presence of epinephrine; The results indicate that the mechanisms wh ereby hormones and lipoproteins activate phosphoinositides turnover ar e similar and may involve G-proteins.