Interaction of β-very-low-density lipoproteins with rat liver cells.

Cholesteryl-ester-fich very-low-density lipoproteins (β-VLDL) are considered to be atherogenic because in vitro they can provoke cholesterol accumulation in macrophages. The greatest population ofmacrophages resides inside the liver and in the present study the rat β-VLDL uptake by the various rat liver cell types is determined in vivo and compared to the uptake of rat VLDL. β-VLDL isolated from cholesterol-fed rats was iodinated and injected into the rat. After 10 min of circulation, 45% of the injected β-VLDL was found in the liver. A low-temperature cell-isolation procedure shows that rat liver parenchymal cells form the major site for β-VLDL uptake (96%) and, consequently, rat liver macrophages (nonparenchymal liver cells) do not perform a quantitatively significant role in the uptake of these lipoproteins. In vitro competition studies indicate that apolipoprotein (apo) E is the site recognised by liver parechymal cells and even a 600-fold excess of apo-E-free human LDL was an ineffective competitor. Furthermore it can be demonstrated that induction of apo-B,E receptors on liver parenchymal cells by estrogen treatment does not result in a significant increased uptake of β-VLDL. These data show that recognition of β-VLDL is presumably exerted by the remnant receptor. Intracellular processing of both the apolipoproteins and phospholipids of β-VLDL was followed by subcellular distribution studies. It appears that, within 45 min, 75% of the apolipoproteins are degraded and subsequently released from the liver. In contrast the phospholipids remain associated with the liver for a prolonged time and a specific transfer to the mitochondrial fraction is found. It can be concluded that liver parenchymal cells form in vivo the major site for β-VLDL uptake and it appears that recognition of β-VLDL is coupled to internalization and processing of both the apolipoproteins and phospholipids by a route which involves the lysosomes. [ABSTRACT FROM AUTHOR]