Semicarbazide-sensitive amine oxidase catalyzes endothelial cell-mediated low density lipoprotein oxidation.
OBJECTIVE
Deamination products of semicarbazide-sensitive amine oxidases (SSAO), i.e. aldehydes, superoxide and ammonia have been shown to initiate vascular damage. SSAOs are copper-enzymes, present in endothelial (EC), smooth muscle cells (SMC) and in blood. Transition metals ions (Cu, Fe) mediate the oxidative (atherogenic) modification of LDL by SMC and EC. The physiological source of the active metal ions is still under debate. We hypothesize that SSAOs may catalyze LDL oxidation by endothelial cells via enzyme-complexed Cu++.


METHODS
EC isolated from human umbilical veins and cultured in 35 mm wells in RPMI-1640 medium were used as LDL oxidation system.


RESULTS
Diamine oxidase (DAO), a SSAO which activity is elevated in tissues and sera of diabetic patients, catalyzes the oxidation of LDL by EC. In the presence of purified DAO (0.07 to 70 U/l) LDL oxidation was increased up to 10-fold as measured by thiobarbituric acid reactive substance (TBARS) formation as well as apoprotein modification of LDL. Chemical blockage of the SSAO substrate binding site did not inhibit the catalytic effect of DAO on LDL oxidation. Denaturation of the enzyme did not destroy the ability of the preparation to facilitate LDL oxidation by EC. The potential of the enzyme to catalyze LDL oxidation was not suppressed in the presence of serum. However, selective removing of enzyme-copper completely abolished the ability of the enzyme to trigger cell-mediated LDL oxidation.


CONCLUSIONS
DAO, beside generating angiopathic deamination products, has the potential to act as a pathophysiological catalyst of LDL atherogenic modification by vascular cells.
Exner
M
M
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria.
Hermann
M
M
Hofbauer
R
R
Kapiotis
S
S
Quehenberger
P
P
Speiser
W
W
Held
I
I
Gmeiner
B M
BM
D006631:Amine Oxidase (Copper-Containing) / Q000494:pharmacology*; D002384:Catalysis; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction
D008077:Lipoproteins, LDL; D006631:Amine Oxidase (Copper-Containing)