LYSOPHOSPHATIDYLCHOLINE CAUSES CA2-SYNTHESIS AND CYTOTOXICITY IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS( INFLUX, ENHANCED DNA)

The effects of lysophosphatidylcholine (LPC), a vasoactive phospholipi d, on intracellular free calcium concentration ([Ca2+](i)), DNA synthe sis and cytotoxicity of vascular smooth muscle cells (VSMC) were studi ed. LPC from 10(-7) to 10(-5) mol/l dose-dependently induced a sustain ed increase in [Ca2+](i). In contrast to the response of [Ca2+](i) ind uced by angiotensin II, that induced by LPC was totally abolished when extracellular Ca2+ was removed, was not affected by pretreatment of t he cells with islet-activating protein, and was not desensitized by re peated addition. 8-(N,N-Diethylamino)octyl 3,4,5-trimethoxybenzoic aci d (TMB-8), an inhibitor of Ca2+ release from intracellular Ca2+ stores , 1-(5-isoquinolinesulfonyl)-2-methylpiperadine dihydrochloride (H-7), an inhibitor of protein kinase C, KT5823, an inhibitor of protein kin ase G, and Ca2+ channel blockers failed to suppress the LPC-induced in crease in [Ca2+](i). LPC at 10(-5) mol/l caused significant stimulatio n of [H-3]thymidine incorporation into VSMC, and at concentrations of 10(-5) mol/l and higher dose-dependently stimulated release of lactate dehydrogenase in cell culture supernatants. Moreover, digitonin mimic ked the effects of LPC on [Ca2+](i), and also caused similar effects t o those of LPC on DNA synthesis and cytotoxicity in VSMC. These observ ations suggest that LPC causes both cell growth and cell injury of VSM C, at least partly, through its detergent action, causing membrane lea kiness and resultant [Ca2+](i) overload in vitro, thus indicating the possible participation of LPC in atherosclerosis and/or injury of the vascular wall.