Inhibitors of arterial relaxation among components of human oxidized low-density lipoproteins: cholesterol derivatives oxidized in position 7 are potent inhibitors of …

V Deckert, L PerseŽ gol, L Viens, G Lizard, A Athias… - Circulation, 1997 - Am Heart Assoc
V Deckert, L PerseŽ gol, L Viens, G Lizard, A Athias, C Lallemant, P Gambert, L Lagrost
Circulation, 1997Am Heart Assoc
Background Oxidized low-density lipoproteins (LDLs) are known to impair arterial relaxation.
The aim of the present study was to identify the components of oxidized LDL that may
account for inhibition of endothelium-dependent relaxation. Methods and Results LDLs from
12 healthy subjects were either maintained at 4° C (native LDL) or incubated at 37° C in the
presence of copper sulfate (oxidized LDL). Unlike pretreatment with native LDL,
pretreatment with oxidized LDL reduced significantly the acetylcholine-mediated relaxation …
Background Oxidized low-density lipoproteins (LDLs) are known to impair arterial relaxation. The aim of the present study was to identify the components of oxidized LDL that may account for inhibition of endothelium-dependent relaxation.
Methods and Results LDLs from 12 healthy subjects were either maintained at 4°C (native LDL) or incubated at 37°C in the presence of copper sulfate (oxidized LDL). Unlike pretreatment with native LDL, pretreatment with oxidized LDL reduced significantly the acetylcholine-mediated relaxation of rabbit aortic segments compared with control segments incubated in Krebs' buffer (maximal relaxation [Emax], 72.0±6.7% versus 94.1±0.8%, respectively, P<.01; negative logarithm of the concentration required to produce a half-maximal relaxing effect [pD2], 6.6±0.1 versus 7.2±0.1, respectively, P<.001). The absolute difference between Emax values obtained with oxidized and native LDL (ΔEmax) correlated significantly with the formation of 7-ketocholesterol, 7α-hydroxycholesterol, and 7β-hydroxycholesterol. In contrast, ΔEmax did not correlate with the amount of lipoperoxides or lysophosphatidylcholine formed, and the difference of pD2 values measured with oxidized and native LDL (ΔpD2) did not correlate significantly with any of the oxidation-derived LDL compounds. When added individually, 7-ketocholesterol and 7β-hydroxycholesterol reduced Emax values but not pD2 values in a time- and concentration-dependent manner.
Conclusions Cholesterol derivatives in oxidized LDL can reduce maximal arterial relaxation through a specific effect on vascular endothelial cells.
Am Heart Assoc