Redox-sensitive impairment of porcine coronary artery vasodilation by hypochlorite-modified LDL.
Atherosclerotic vascular disease is associated with abnormal vasomotor function and oxidized low density lipoproteins (OxLDL) are believed to play a keyrole therein. Several compounds emerging from LDL lipid peroxidation have been shown to be able to alter vasomotion but the role of oxidized apoB in this process is not fully understood. Myeloperoxidase has been identified in atherosclerotic lesions and hypochlorite produced by this enzyme represents a strong oxidant. LDL oxidation by hypochlorite differs from most other forms of LDL oxidation in that hypochlorite-mediated oxidation shows a predilection for the protein moiety of LDL and does not result in lipid peroxidation. In this work, we use porcine coronary artery segments and show that hypochlorite-oxidized LDL (hyp-OxLDL) are able to impair dilatation induced by substance P in a dose- and modification-dependent way. Treatment of hyp-OxLDL with methionine resulted in quantitative elimination of reactive chloramines in LDL and complete recovery of relaxation. As application of the scavenger receptor antagonist maleylated albumin strongly interferes with the effects of hyp-OxLDL on vasomotion, we conclude that specific binding of hypochlorite-modified apoB is likely to be involved in mediating the observed effects.
Plass
Christian A
CA
Institute of Physiology, Center for Physiology & Pathophysiology, Medical University of Vienna, Schwarzspanierstr 17, A-1090 Vienna, Austria.
Schmid
Werner
W
Holy
Erik W
EW
Kreatschitsch
Ursula
U
Laggner
Hildegard
H
Volf
Ivo
I
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D008077:Lipoproteins, LDL; D014662:Vasoconstrictor Agents; D006997:Hypochlorous Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid