A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis.

IN recent years, a marked increase in knowledge about the levels of circulating lipoprotein classes, their structural components, and physical organization has taken place. A new appreciation of the dynamic metabolism of lipoproteins in humans and in experimental animals has been gained from studies of the various nascent lipoproteins, the sequential steps of lipolysis that take place among and give rise to circulating lipoproteins, and the various exchanges of constituents among classes. It is not possible to do more than summarize major advances, but several recent excellent reviews may be consulted for details (Smith et al., 1978; Fredrickson et al., 1978; Schaefer et al., 1978a). Triglyceride-rich very low density lipoproteins (VLDL) are secreted by the liver and to some degree by the intestine and are acted on by lipoprotein lipase (LPL), leading to progressive lipolysis, loss of triglyceride, and conversion to a smaller cholesterol ester (and cholesterol)-rich lipoprotein class known as low density lipoprotein (LDL). Chylomicrons are large fat-containing particles resulting from intestinal absorption of dietary fat and through a similar action of LPL are converted to so-called "remnant" particles, rich in esterified and free cholesterol. Another class of lipoprotein, high density lipoproteins (HDL), apparently is derived from both intestinal and hepatic sources. HDL not only exchange certain proteins and phospholipids with VLDL, but also apoprotein C-II of the subclass of HDL called HDL2 seems to activate LPL, thereby favoring the conversion of VLDL to LDL (Fredrickson et al., 1978; Tall and Small, 1978).