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 oxi dized LDL (ox-LDL) in the arterial intima could be derived from LDL al ready oxidized in plasma. Methods and Results Rabbits received an intr avenous injection of I-125-labeled normal LDL (N-LDL) mixed with I-131 -labeled : LDL that had been mildly oxidized through exposure to Cu2+. The aortic accumulation of undegraded labeled LDL was expressed as pl asma equivalents and calculated as radioactivity in the intima/inner m edia (cpm/cm(2)) divided by the time-averaged concentration of radioac tivity in plasma (cpm/nL): for the thoracic aorta, the accumulation of undegraded ox-LDL in the intima/inner media exceeded that of undegrad ed 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 stro ng 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, I-125-LDL labeled with I-131-tyramine cellobiose was injected intravenously 24 hours before: the aortic intima/inner me dia was removed: for the thoracic aorta, the accumulation of degradati on 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 t o enter, accumulate, and be degraded in the arterial intima in prefere nce to N-LDL.