Oxidation of plasma low-density lipoprotein accelerates its accumulation and degradation in the arterial wall in vivo.
BACKGROUND
The aim of the present study was to investigate whether oxidized LDL (ox-LDL) in the arterial intima could be derived from LDL already oxidized in plasma.


RESULTS
Rabbits received an intravenous injection of 125I-labeled normal LDL (N-LDL) mixed with 131I-labeled LDL that had been mildly oxidized through exposure to Cu2+. The aortic accumulation of undegraded labeled LDL was expressed as plasma equivalents and cakulated as radioactivity in the intima/inner media (cpm/cm2) divided by the time-averaged concentration of radioactivity in plasma (cpm/nL): for the thoracic aorta, the accumulation of undegraded ox-LDL in the intima/ inner media exceeded that of undegraded N-LDL by 286% (n = 6, P < .04), 863% (n = 7, P < .02), and 364% (n = 8, P < .01) after 1, 3, and 24 hours of exposure, respectively. There was a strong positive association between the extent of oxidation and the excess accumulation of undegraded ox-LDL compared with N-LDL (thoracic aorta; 3 hours of exposure: r = .97, n = 14, P < .00001). To measure degradation of N-LDL and ox-LDL, 125I-LDL labeled with 131I-tyramine cellobiose was injected intravenously 24 hours before the aortic intima/inner media was removed: for the thoracic aorta, the accumulation of degradation products from ox-LDL (n = 6) exceeded that from N-LDL (n = 6) by 301% (P < .04).


CONCLUSIONS
The present data suggest a novel mechanism: mildly oxidized LDL may circulate in plasma for a period sufficiently long to enter, accumulate, and be degraded in the arterial intima in preference to N-LDL.
Juul
K
K
Department of Clinical Biochemistry, Rigshospitalet, Denmark.
Nielsen
L B
LB
Munkholm
K
K
Stender
S
S
Nordestgaard
B G
BG
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits; D014018:Tissue Distribution; D017539:Tunica Intima / Q000378:metabolism; D017540:Tunica Media / Q000378:metabolism
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein