THE INJECTION OF HEPARIN PROLONGS THE PLASMA-CLEARANCE OF OXIDIZED LOW-DENSITY-LIPOPROTEIN IN THE RAT

There is evidence that oxidized-LDL plays an important role in atherog enesis. We now report on the in vivo interaction between unfractionate d heparin and oxidized LDL in rats. The recovery rates of the native L DL particles ranged between 75% and 85% of the injected dose. Heparin did not interfere with the clearance rates of native LDL. After admini stration of radioactive labeled oxidized-LDL particles, 26% of the mat erial was measured in circulation after 5 minutes, 8% after 20 minutes , and 3% after 60 minutes. After injection of heparin 2 minutes prior to oxidized-LDL tracer particles, 44% of the tracer was found in blood after 5 minutes, 23% after 20 minutes, and 9% after 60 minutes. Oxidi zed-LDL tracer particles disappeared from blood with an alpha half-lif e of 5 minutes and a beta half-life of 7.5 minutes. After receptor blo cking with unfractionated heparin the alpha half-life of the oxidized- LDL tracer was prolonged to 17.5 minutes and the beta half-life to 27. 5 minutes. These results indicate that heparin molecules of a comparat ively small molecular weight competed the scavenger receptor mediated uptake of oxidized-LDL particles in vivo. Oxidized-LDL particles are k nown to mediate their pro-atherosclerotic activity in part by stimulat ing smooth muscle cell proliferation by a scavenger receptor-mediated pathway. It can be speculated, if heparins interfere with the uptake o f oxidized-LDL, heparins might thus in part exert their known antiathe rosclerotic properties.