[Involvement of endothelin in the proliferative effect of lysophosphatidic acid on vascular smooth muscle cells in rats].
OBJECTIVE
To observe the effects of lysophosphatidic acid (LPA) on production of endothelin (ET) in rat aorta vascular smooth muscle cells (VSMCs).


METHODS
Cultured VSMCs were used in the study. DNA synthesis of VSMCs was measured by 3H-TdR incorporation. The amount of ET mRNA of VSMCs was determined by competitive quantitative RT-PCR. The levels of synthesis and release of ET in VSMCs were determined by radioimmunoassay (RIA).


RESULTS
5-20 mumol.L-1 of LPA promoted VSMCs 3H-TdR incorporation in a concentration dependent manner. The amount of ET mRNA in VSMCs treated by 5-20 mumol.L-1 of LPA was increased by 16%, 21%, and 23%, respectively, compared with the control. After 8 hours of incubation, 5-20 mumol.L-1 of LPA elevated the ET production in a concentration dependent manner. After 8 hours of VSMCs incubated with LPA (5-20 mumol.L-1), the content of ET in medium was increased by 140%-200%, respectively, compared with the control. In addition, it was found that BQ123, a non-selective ET receptor antagonist, greatly decreased the VSMCs DNA synthesis induced by LPA.


CONCLUSIONS
LPA stimulated the ET mRNA expression and ET production in VSMCs. The effects of LPA on VSMCs DNA synthesis were partly mediated by ET/ETA receptor pathway. It suggests that LPA and ET interact and exert biological effects as endogenous active peptides.
Institute of Cardiovascular Diseases Research, Peking University First Hospital, Beijing 100034, China.
Yongsheng
Y
Ren
Chunshui
C
Pan
Qizhuan
Q
Wu
Yongzheng
Y
Pang
Chaoshu
C
Tang
Yongfen
Y
Qi
D000818:Animals; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D010455:Peptides; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D051381:Rats
D016232:Endothelins; D008246:Lysophospholipids; D010455:Peptides; D010456:Peptides, Cyclic; D012333:RNA, Messenger; C032881:lysophosphatidic acid; C072247:cyclo(Trp-Asp-Pro-Val-Leu)