Effects of the heparin-mimicking compound RG-13577 on lipoprotein lipase and on lipase mediated binding of LDL to cells

Lipoprotein lipase (LPL) has high affinity for heparin and heparin-like com pounds. In vivo the enzyme is attached to heparan sulfate proteoglycans on the endothelium of capillaries and larger blood vessels. The enzyme is rele ased from these sites after intravenous injection of heparin. One has hen i nvestigated the effects of RG-13577 on LPL, both after intravenous injectio n to rats and under cell culture conditions. RG-13577 is a heparin-mimickin g compound known to prevent angiogenesis by interference with binding of gr owth factors to cells. It has therefore been considered for use in cancer t herapy as well as for prevention of atherosclerosis and restenosis. It was found that intravenously injected RG-13577 released both LPL and hepatic li pase (HL) to the blood. Binding of LPL in extrahepatic tissues was prevente d and clearance of radiolabeled LPL from the circulation was delayed. Furth ermore, RG-13577 released LPL from extracellular matrix (ECM) produced by e ndothelial cells and from THP-I monocyte-derived macrophages. Lipase-mediat ed binding and uptake of human LDL in these cells was also prevented by RG- 13577. Thus, in the test systems RG-13577 had the same effects as heparin, but on a molar basis RG-13577 was in all cases less effective. (C) 2001 Els evier Science Ireland Ltd, All rights reserved.