Oxidized LDL from subjects with different dietary habits modifies atherogenic processes in endothelial and smooth muscle cells.
Low-density lipoprotein (LDL) activates a number of processes involved in atherogenesis and vasoconstriction. Evidence suggests that oxidation increases the atherogenicity of LDL. We investigated the effects of oxidized LDL (ox-LDL) on cytotoxicity, prostacyclin (PGI2), 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-mediated LDL oxidation. Native LDL (n-LDL) was isolated from subjects on three long-term diets with differing fatty acid content (control diet rich in saturated fat and vegetarian and fish diets). The Cu2+-catalyzed oxidation of n-LDL was monitored using conjugated diene formation and stopped at various time points to achieve 20%, 45%, 70%, and 100% levels of ox-LDL. The lag phase of oxidation by Cu2+ was shortest and thiobarbituric acid-reactive substance (TBARS) formation by VSMC-mediated oxidation was highest with n-LDL obtained from the fish diet group. There were no differences between the ox-LDLs obtained from the different diet groups in their cytotoxicity in EC culture. The degree of oxidation did not influence LDL cytotoxicity. In VSMC culture PGI2 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 PGI2 production. The LDLs did not affect basal cGMP production in either EC or VSMC culture.
Lähteenmäki
T A
TA
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. tuula.lahteenmaki@helsinki.fi
Seppo
L
L
Laakso
J
J
Korpela
R
R
Vanhanen
H
H
Tikkanen
M J
MJ
Vapaatalo
H
H
D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019327:Copper Sulfate / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D014676:Diet, Vegetarian; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005227:Fatty Acids / Q000008:administration & dosage / Q000032:analysis; D005247:Feeding Behavior / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017747:Seafood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D004041:Dietary Fats; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D011464:Epoprostenol; D006152:Cyclic GMP; D019327:Copper Sulfate