Inhibitors of arterial relaxation among components of human oxidized low-density lipoproteins. Cholesterol derivatives oxidized in position 7 are potent inhibitors of endothelium-dependent 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.


RESULTS
LDLs from 12 healthy subjects were either maintained at 4 degrees C (native LDL) or incubated at 37 degrees 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 (delta Emax) correlated significantly with the formation of 7 ketocholesterol, 7 alpha-hydroxycholesterol, and 7 beta-hydroxy-cholesterol. In contrast, delta Emax did not correlate with the amount of lipoperoxides or lysophosphatidylcholine formed, and the difference of pD2 values measured with oxidized and native LDL (delta pD2) did not correlate significantly with any of the oxidation-derived LDL compounds. When added individually, 7-ketocholesterol and 7 beta-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.
Deckert
V
V
Laboratoire de Biochimie des Lipoprotéines, INSERM CJF 93-10, Faculté de Médecine, Dijon, France.
Perségol
L
L
Viens
L
L
Lizard
G
G
Athias
A
A
Lallemant
C
C
Gambert
P
P
Lagrost
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002784:Cholesterol / Q000031:analogs & derivatives*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007653:Ketocholesterols / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D009599:Nitroprusside; D002784:Cholesterol; D000109:Acetylcholine; C003001:7-ketocholesterol