Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta.
Lysophosphatidic acids (LPA) with a C18 fatty acyl group accelerated thymidine incorporation into cultured rat aortic vascular smooth muscle cells and stimulated their cell division. LPA acted synergistically with epidermal growth factor and fibroblast growth factor but additively with platelet-derived growth factor. The stimulatory actions of LPA were suggested to be rather specific from the following findings: 1) their stimulation of DNA synthesis increased with an increase in their acyl moiety; 2) lysophosphatidylcholine, a neutral lysophospholipid, had no mitogenic action but was cytotoxic at high concentrations; and 3) LPA induced a rapid external Ca(2+)-independent increase in intracellular Ca2+ concentration ([Ca2+]i) in single fura 2-loaded cells that resembled the receptor-mediated increases in [Ca2+]i triggered by different agonists, whereas lysophosphatidylcholine provoked a slow sustained increase in [Ca2+]i in an external Ca(2+)-dependent manner. These results are discussed in relation to the possible pathophysiological role of LPA.
Tokumura
A
A
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Iimori
M
M
Nishioka
Y
Y
Kitahara
M
M
Sakashita
M
M
Tanaka
S
S
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D008934:Mitogens; D004247:DNA; D002118:Calcium