Oxidized low-density lipoproteins in atherogenesis: possible mechanisms of action.
The increased atherogenic potential of oxidized low-density lipoprotein (ox-LDL) is well documented. In the present study, we investigated possible mechanisms of action of the difference to native LDL. In vitro oxidation of LDL was determined by measurement of thiobarbituric acid-reacting substances and absorption at 234 nm. Copper (5 mumol/L) induced significant (p less than 0.01) oxidation in vitro. Furthermore, LDL isolated from atherosclerotic patients was slightly but significantly (p less than 0.05) more oxidized than LDL from normal controls (2.81 +/- 0.08 vs. 3.21 +/- 0.16 nmol of TBARS/mg of LDL protein). Ox-LDL caused significantly (p less than 0.01) more pronounced contractions of rat aortic rings in vitro compared to nonoxidized LDL expressed as a percentage of maximal contractions induced by 40 mmol/L of KCl (29.0 +/- 5.4% vs. 61.1 +/- 7.2%). Lysolecithin, which is a principal component of ox-LDL formed during oxidation, induced a dose-dependent increase in intracellular free calcium in vascular smooth muscle cells cultured from rat aorta. Doses from 2-25 micrograms/ml were tested and caused a maximum increase of more than 500% (25 micrograms/ml). In conclusion, this study provides further evidence for a higher biological activity of ox-LDL. Lysolecithin might be one of the active components formed during oxidation of LDL.
Weisser
B
B
Department of Internal Medicine, University Hospital Zürich, Switzerland.
Locher
R
R
Mengden
T
T
Sachinidis
A
A
Vetter
W
W
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011921:Rats, Inbred WKY
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines