Ta. Lahteenmaki et al., Oxidized LDL from subjects with different dietary habits modifies atherogenic processes in endothelial and smooth muscle cells, LIFE SCI, 66(5), 2000, pp. 455-465
Low-density lipoprotein (LDL) activates a number of processes involved in a
therogenesis and vasoconstriction. Evidence suggests that oxidation increas
es the atherogenicity of LDL. We investigated the effects of oxidized LDL (
ox-LDL) on cytotoxicity, prostacyclin (PGI(2)), and cyclic guanosine-3 ',5'
-monophosphate (cGMP) production in rat vascular smooth muscle cell (VSMC)
and rat heart endothelial cell (EC) culture, as well as EC- and VSMC-mediat
ed LDL oxidation. Native LDL (n-LDL) was isolated from subjects on three lo
ng-term diets with differing fatty acid content (control diet rich in satur
ated fat and vegetarian and fish diets). The Cu2+-catalyzed oxidation of n-
LDL was monitored using conjugated diene formation and stopped at various t
ime points to achieve 20%, 45%, 70%, and 100% levels of ox-LDL. The lag pha
se of oxidation by Cu2+ was shortest and thiobarbituric acid-reactive subst
ance (TBARS) formation by VSMC-mediated oxidation was highest with n-LDL ob
tained from the fish diet group. There were no differences between the ox-L
DLs obtained from the different diet groups in their cytotoxicity in EC cul
ture. The degree of oxidation did not influence LDL cytotoxicity. In VSMC c
ulture PGI(2) production was increased by ox-LDLs from all diet groups. In
EC culture only the extensively oxidized LDLs obtained from the vegetarian
diet group were able to induce PGI(2) production. The LDLs did not affect b
asal cGMP production in either EC or VSMC culture.