Lysophosphatidylcholine causes Ca2+ influx, enhanced DNA synthesis and cytotoxicity in cultured vascular smooth muscle cells.
The effects of lysophosphatidylcholine (LPC), a vasoactive phospholipid, on intracellular free calcium concentration ([Ca2+]i), DNA synthesis and cytotoxicity of vascular smooth muscle cells (VSMC) were studied. LPC from 10(-7) to 10(-5) mol/l dose-dependently induced a sustained increase in [Ca2+]i. In contrast to the response of [Ca2+]i induced by angiotensin II, that induced by LPC was totally abolished when extracellular Ca2+ was removed, was not affected by pretreatment of the cells with islet-activating protein, and was not desensitized by repeated addition. 8-(N,N-Diethylamino)octyl 3,4,5-trimethoxybenzoic acid (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 kinase G, and Ca2+ channel blockers failed to suppress the LPC-induced increase in [Ca2+]i. LPC at 10(-5) mol/l caused significant stimulation of [3H]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 mimicked the effects of LPC on [Ca2+]i, and also caused similar effects to those of LPC on DNA synthesis and cytotoxicity in VSMC. These observations suggest that LPC causes both cell growth and cell injury of VSMC, at least partly, through its detergent action, causing membrane leakiness and resultant [Ca2+]i overload in vitro, thus indicating the possible participation of LPC in atherosclerosis and/or injury of the vascular wall.
Chen
Y
Y
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Morimoto
S
S
Kitano
S
S
Koh
E
E
Fukuo
K
K
Jiang
B
B
Chen
S
S
Yasuda
O
O
Hirotani
A
A
Ogihara
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D008244:Lysophosphatidylcholines; D004247:DNA; D007770:L-Lactate Dehydrogenase; D002118:Calcium