Endothelial dysfunction induced by oxidized low-density lipoproteins in isolated mouse aorta: a comparison with apolipoprotein-E deficient mice.
We characterized the acute effects of oxidized low-density lipoproteins (oxidized-LDL) on vascular reactivity in isolated aorta from wild-type C57BL/6J mice, and compared these with the chronic alterations in vascular function observed in apolipoprotein-E gene knockout [ApoE(-/-)] mice fed a high-fat diet, which results in hyperlipidemia and atherosclerosis. In the abdominal (but not thoracic) aorta, oxidized-LDL (100 microg/ml) reduced relaxations induced by acetylcholine (10(-9) M-10(-5) M), which are mediated entirely by nitric oxide (NO). The relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) M-10(-4) M), the cyclic GMP analogue 8-bromo cyclic GMP (100 microM) and the nonspecific vasodilator papaverine (100 microM) were not changed by oxidized-LDL. Native LDL had no effect on vasorelaxations. The attenuation of endothelium-dependent relaxations caused by oxidized-LDL mimicked the endothelial dysfunction found in ApoE(-/-) mice. These results are consistent with the suggestion that oxidized-LDL has an important role in the pathogenesis of endothelial NO dysfunction associated with hyperlipidemia and atherosclerosis in these mice.
Jiang
F
F
Howard Florey Institute, The University of Melbourne, Victoria, 3010, Australia. f.jiang@hfi.unimelb.edu.au
Gibson
A P
AP
Dusting
G J
GJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005838:Genotype; D006949:Hyperlipidemias / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010396:Penicillamine; D000109:Acetylcholine; D011188:Potassium