title: Oxidation of low density lipoprotein enhances its potential to increase intracellular free calcium concentration in vascular smooth muscle cells.
abstract: There have been suggestions that oxidation of low density lipoproteins (LDL) might increase their atherogenic potential. Because changes in intracellular free calcium concentration [Ca2+]i have been linked to atherogenesis, we compared the influence of oxidized LDL (Ox-LDL) and native LDL (N-LDL) on [Ca2+]i in vascular smooth muscle cells cultured from rat aortas. For determination of [Ca2+]i, fura-2 fluorescence was used. LDL was isolated by ultracentrifugation from the sera of human donors (n = 17). In N-LDL, oxidation was prevented by addition of antioxidants, whereas Ox-LDL was obtained by auto-oxidation. The extent of oxidation was assessed by measurement of thiobarbituric acid-reactive substances. Addition of Ox-LDL (20 micrograms protein/ml) to the vascular smooth muscle cells induced a mean increase of 129 +/- 13% in [Ca2+]i compared with 81 +/- 7% with N-LDL (p less than 0.01). Dose-response curves from 1 to 20 micrograms/ml (six experiments) confirmed this difference within the entire dose range. These results indicate that a more pronounced increase in [Ca2+]i induced by Ox-LDL might be one of the cellular mechanisms responsible for the higher atherogenic potential of Ox-LDL compared with N-LDL, as [Ca2+]i is an important second-messenger system involved in many atherogenic processes such as hypertrophy, cell migration, and cell damage.
authors.affiliation: Department of Internal Medicine, University Hospital, Zürich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Weisser
authors.forename: R
authors.initials: R
authors.lastname: Locher
authors.forename: T
authors.initials: T
authors.lastname: Mengden
authors.forename: W
authors.initials: W
authors.lastname: Vetter
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D008077:Lipoproteins, LDL; D002118:Calcium