Mt. Lin et al., The various effects of fractionated oxidized low density lipoproteins on the growth of smooth muscle cells in culture, J BIOMED SC, 6(4), 1999, pp. 260-268
The effects of fractionated oxidized low density lipoproteins (oxidized LDL
) on the growth of vascular smooth muscle cells (VSMC) and their relationsh
ip to the formation of lysophosphatidylcholine (lyso-PC) as well as the act
ivation of protein kinase C (PKC) were studied, VSMC were isolated from por
cine aorta by explant culture. LDL was isolated from porcine blood by seque
ntial ultracentrifugation and oxidized LDL was obtained by incubating LDL w
ith 5 mu M CuSO4 at 37 degrees C for various lengths of time. Our results s
howed that LDL oxidized for 12 h and eluted from fast protein liquid chroma
tography at 43 min inhibited the growth of VSMC, and that LDL oxidized for
longer than 48 h and eluted at 48 min stimulated the growth of VSMC, The fo
rmation of lyse-PC in the oxidized LDL correlated well with its stimulatory
effect, suggesting that lyse-PC is responsible for the mitogenic effect of
oxidized LDL. This stimulatory effect of oxidized LDL was inhibited by sta
urosporine, a PKC inhibitor. Treatment with oxidized IDL increased the acti
vity of membrane PKC, but it decreased that of cytosolic PKC, suggesting th
e translocation of PKC from cytosol to the membrane in the presence of oxid
ized LDL. These results suggested that the oxidized LDL-stimulated VSMC gro
wth was mediated by the formation of lyse-PC and the activation of PKC.