Suppression by eicosapentaenoic acid of oxidized low-density lipoprotein and lysophosphatidylcholine-induced migration in cultured rat vascular smooth muscle cells.
The migration of medial smooth muscle cells into the intima is proposed to be an initial process of intimal thickening in atherosclerotic lesions. The present study was designed to determine whether pretreatment with the antiatherogenic agent eicosapentaenoic acid (EPA) inhibits the migration induced by oxidized low-density lipoprotein (LDL) and its major phospholipid component, lysophosphatidylcholine (lyso-PC), in cultured rat vascular smooth muscle cells (VSMCs) using Boyden's chamber method. The effects of EPA pretreatment on angiotensin II (Ang II)- and platelet-derived growth factor BB (PDGF BB)-induced migration were also examined in these cells. Oxidized LDL and lyso-PC induced migration in a concentration-dependent manner. EPA pretreatment clearly suppressed oxidized LDL (200 microg/mL)- and lyso-PC (10(-5) mol/L)-induced migration between 40 and 160 micromol/L. EPA pretreatment also suppressed Ang 11 (10(-7) mol/L)- and PDGF BB (5 ng/mL)-induced migration at a concentration of 80 and 160 micromol/L. However, in a trypan blue exclusion test, dead cells stained with trypan blue were not found 24 hours after treatment with EPA. These results suggest that EPA suppresses VSMC migration induced by oxidized LDL and lyso-PC, as well as Ang II and PDGF BB. These preliminary data concerning the effects of EPA may partly explain the antiatherosclerotic effects of this agent.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Yasunari
K
K
Minami
M
M
Kano
H
H
Maeda
K
K
Yoshikawa
J
J
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors*; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein; D015118:Eicosapentaenoic Acid