(Circulation. 1996;94:1698-1704.)
© 1996 American Heart Association, Inc.
Articles |
Oxidation of Plasma Low-Density Lipoprotein Accelerates Its Accumulation and Degradation in the Arterial Wall In Vivo
the Department of Clinical Biochemistry (K.J., L.B.N., K.M.), Rigshospitalet, and Department of Clinical Biochemistry (B.G.N.), Herlev Hospital, University of Copenhagen, Denmark; and Clinical Institute (S.S.), University of Odense, Denmark.
Correspondence to Dr Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev Hospital, DK-2730 Herlev, Denmark.
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.
Methods and 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 calculated 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.
Key Words: atherosclerosis • lipoproteins
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