Y. Chen et al., LYSOPHOSPHATIDYLCHOLINE CAUSES CA2-SYNTHESIS AND CYTOTOXICITY IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS( INFLUX, ENHANCED DNA), Atherosclerosis, 112(1), 1995, pp. 69-76
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.