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. Methods and Results Rabbits received an intravenous 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 plasma equivalents and calculated as radioactivity in the intima/inner media (cpm/cm(2)) 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, I-125-LDL labeled with I-131-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.