LDL RECEPTOR FAMILY-DEPENDENT AND FAMILY-INDEPENDENT PATHWAYS FOR THEINTERNALIZATION AND DIGESTION OF LIPOPROTEIN LIPASE-ASSOCIATED BETA-VLDL BY RAT VASCULAR SMOOTH-MUSCLE CELLS

Lipoprotein lipase (LPL) promotes the binding and internalization of b eta-VLDL (very low density lipoprotein) by many cell types. We examine d the function of receptors in the LDL receptor family (LRF) and hepar an sulfate proteoglycans (HSPG) in the metabolism of LPL-associated be ta-VLDL by rat vascular smooth muscle cells (VSMCs) in culture. These cells express LDL receptor-related protein and the VLDL receptor, but not the LDL receptor. LPL greatly increased the binding of I-125-label ed beta-VLDL to VSMCs at 4 degrees C. Binding was almost entirely inhi bited by heparin, but essentially unaffected by the potent LRF-antagon ist, receptor-associated protein (RAP), indicating that LRFs do not co ntribute significantly to the VSMC binding capacity for LPL-associated beta-VLDL. At 37 degrees C, RAP inhibited the rapid internalization o f LPL-associated I-125-labeled beta-VLDL and the digestion of the beta -VLDL into trichloroacetic acid soluble radioactivity; these processes still occurred, but at a decreased rate. RAP did not inhibit the abil ity of beta-VLDL-LPL complex to stimulate VSMC ACAT activity. Furtherm ore, in Oil red-O histochemistry experiments, which model foam cell tr ansformation in vitro, RAP paradoxically increased cholesteryl ester s torage in VSMCs treated with beta-VLDL and LPL under specific cell cut tune conditions. These results support a model in which the internali zation of LPL-associated beta-VLDL by VSMCs is mediated by two pathway s, one involving LRFs and a second that is independent of LRFs, probab ly involving direct uptake by HSPG. The LRF-dependent pathway leads to less cellular storage of cholesteryl ester and thus may be antiathero genic under certain conditions.