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 atherogenesis. We now report on the in vivo interaction between unfractionated heparin and oxidized LDL in rats. The recovery rates of the native LDL particles ranged between 75% and 85% of the injected dose. Heparin did not interfere with the clearance rates of native LDL. After administration of radioactive labeled oxidized-LDL particles, 26% of the material 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. Oxidized-LDL tracer particles disappeared from blood with an alpha half-life of 5 minutes and a beta half-life of 7.5 minutes. After receptor blocking 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 comparatively small molecular weight competed the scavenger receptor mediated uptake of oxidized-LDL particles in vivo. Oxidized-LDL particles are known to mediate their pro-atherosclerotic activity in part by stimulating smooth muscle cell proliferation by a scavenger receptor-mediated pathway. It can be speculated, if heparins interfere with the uptake of oxidized-LDL, heparins might thus in part exert their known antiatherosclerotic properties.
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood; D006207:Half-Life; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D008077:Lipoproteins, LDL; D006493:Heparin