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Association between circulating oxidized low density lipoprotein-levels and left ventricular hypertrophy in patients with essential hypertension
Posters 15. Oxidation
115
IP270AI VITAMIN
E SUPPLEMENTS IN STANDARD RODENT DIETS DO NOT AFFECT ANTIOXIDANT INTERVENTION TRIALS IN APO-/- MICE: FAILURE OF VITAMIN E TO INHIBIT ATHEROGENESIS AS ASSESSED BY HISTOLOGY IN AORTIC ARCH AND INNOMINATEKXROTJD ARTERIES
J. Sauter', T.A. Sagban’, J. Schrcder’ , J. Dommermuth*, A. Heimann*, 0. Kemp&i*, H.A.
J. Brmmer’ ,
IP273
OXIDIZED LOW-DENSITY LIPOPROTEIN INDUCES CALCIUM INFLUX IN POLYMORPHONUCLEAR LEUKOCYTES
L.J.H. van Tits, H. Hak-Lemmers, P.N.M. Demacker, A.F.H. Stalenhoef, P.H.G.M. Willems. Departments of Gene& Internal Medicine and Biochemistry. University Medical CenteK Nijmegen, The Netherlands Purpose of the Study: Polymorphonuclear leukocytes (PMN) have been suggested to play a role in atherosclerosis, but intracellular signalling following stimulation with oxidized low density lipoprotein (LDL) is unknown. We investigated mechanistic aspects of oxidized LDL-induced superoxide production by human PMN, with special emphasis on intracellular Ca*’ concentration ([Ca*+]i). Methods: Changes in intracellular Ca2+ concentrations were assessed by monitoring fluorescence of tia 2-acetoxymethylester-loaded cells and superoxide production was measured as peroxidase-catalyzed hnninol-enhanced chemihnninescence. Summary of Results: Oxidized LDL, but not native LDL, evoked an early but sustained increase in [Ca*‘]i and a delayed production of superoxide. The increase in [Ca*‘]i could be reduced by fucoidan and completely prevented by U73 122, suggesting involvement of the scavenger receptor and coupling to the phospholipase C signal transduction pathway. Furthermore, we provide evidence that the increase in [Ca’+]i partly results from protein kinase Cdependent Ca2+ influx. The relevance of this Ca*’ entry for oxidized LDLstimulated effects is illustrated by the fmding that superoxide production was markedly reduced in the absence of external Ca*‘. Finally, inhibition of phagocytosis by cytochalasin B abolished oxidized LDL-stimulated superoxide production without affecting, however, the Ca*’ mobilization. Conclusion: These effects of oxidized LDL on [Ca*+]i and on respiratory burst of PMN may underlie the occurrence of elevated levels of [Ca*+]i of resting PMN in hypercholesterolemia and represent a mechanism by which PMN can amplify processes in the early phase of atherosclerosis. 72nd EAS Congress
115
IP270AI VITAMIN
E SUPPLEMENTS IN STANDARD RODENT DIETS DO NOT AFFECT ANTIOXIDANT INTERVENTION TRIALS IN APO-/- MICE: FAILURE OF VITAMIN E TO INHIBIT ATHEROGENESIS AS ASSESSED BY HISTOLOGY IN AORTIC ARCH AND INNOMINATEKXROTJD ARTERIES
J. Sauter', T.A. Sagban’, J. Schrcder’ , J. Dommermuth*, A. Heimann*, 0. Kemp&i*, H.A.
J. Brmmer’ ,
IP273
OXIDIZED LOW-DENSITY LIPOPROTEIN INDUCES CALCIUM INFLUX IN POLYMORPHONUCLEAR LEUKOCYTES
L.J.H. van Tits, H. Hak-Lemmers, P.N.M. Demacker, A.F.H. Stalenhoef, P.H.G.M. Willems. Departments of Gene& Internal Medicine and Biochemistry. University Medical CenteK Nijmegen, The Netherlands Purpose of the Study: Polymorphonuclear leukocytes (PMN) have been suggested to play a role in atherosclerosis, but intracellular signalling following stimulation with oxidized low density lipoprotein (LDL) is unknown. We investigated mechanistic aspects of oxidized LDL-induced superoxide production by human PMN, with special emphasis on intracellular Ca*’ concentration ([Ca*+]i). Methods: Changes in intracellular Ca2+ concentrations were assessed by monitoring fluorescence of tia 2-acetoxymethylester-loaded cells and superoxide production was measured as peroxidase-catalyzed hnninol-enhanced chemihnninescence. Summary of Results: Oxidized LDL, but not native LDL, evoked an early but sustained increase in [Ca*‘]i and a delayed production of superoxide. The increase in [Ca*‘]i could be reduced by fucoidan and completely prevented by U73 122, suggesting involvement of the scavenger receptor and coupling to the phospholipase C signal transduction pathway. Furthermore, we provide evidence that the increase in [Ca’+]i partly results from protein kinase Cdependent Ca2+ influx. The relevance of this Ca*’ entry for oxidized LDLstimulated effects is illustrated by the fmding that superoxide production was markedly reduced in the absence of external Ca*‘. Finally, inhibition of phagocytosis by cytochalasin B abolished oxidized LDL-stimulated superoxide production without affecting, however, the Ca*’ mobilization. Conclusion: These effects of oxidized LDL on [Ca*+]i and on respiratory burst of PMN may underlie the occurrence of elevated levels of [Ca*+]i of resting PMN in hypercholesterolemia and represent a mechanism by which PMN can amplify processes in the early phase of atherosclerosis. 72nd EAS Congress