338 VANCE & VANCE lipoprotein (LDL), which carries the major portion of cholesterol, as cholesterol ester, in human blood. Conversely, high levels of high density lipoprotein (HDL), which is also enriched in cholesterol ester, appear to lower the risk of heart attack or stroke. Significant progress has been made in understanding the metabolism of lipoproteins, and at the current pace we can expect an even more rapid elucidation of the intricacies of lipoprotein metabolism and its regulation.

The present review is restricted to the assembly and secretion of hepatic lipoproteins. Several recent reviews cover the impressive progress that has been made in understanding the structure of the apoproteins, the structure and expression of the genes that code for these apoproteins, the chromosomal location of these genes, and genetic regulation of apoprotein synthesis (8, 47). Lipoproteins are largely secreted from the liver, although the intestine is the only source of chylomicrons (85) and is a contributor to plasma HDL (24). Space limitations preclude a review of the literature on lipoprotein secretion from the intestine (see 82). Some apolipoproteins, particularly apo E, are secreted by other tissues (eg brain, kidney, spleen) and cells as well as the liver (51). Exactly how important these other tissues are to plasma lipoprotein metabolism is still under investigation (51). It is also beyond the scope of this article to review lipoprotein metabolism in the circulatory system and recep tor-mediated uptake of lipoproteins (see Ref. 9). Lipoprotein assembly and secretion from liver has been studied in intact animals, perfused livers, and cultured hepatocytes. The perfused liver system continues to be a useful model (34). For many experiments cultured primary hepatocytes offer certain advantages as previously noted (20). The cells from a single animal's liver can be investigated under a variety of conditions in a chemically defined medium. Primary rat hepatocytes continue to display many of the functions of liver, including secretion of lipoproteins; the uptake of newly secreted very low density lipoprotein (VLDL) is negligible (20). However, the rat is a poor model for studying some aspects of human lipoprotein metabolism because this rodent has low levels of LDL and is resistant to atherosclerosis. Yet, because it is difficult to induce cardiovascu lar disease, the rat is an interesting animal for comparison with human and primate lipoprotein metabolism. Recently, a human liver tumor-derived cell line, HepG2, has been utilized for studies on lipoprotein secretion (74, 75). Two other human liver-derived cell lines, Hep3B and NPLC, secrete significant amounts of lipoproteins and may be useful for future investi gations (29).