mô gan cũng có các thụ thể LDL phong phú. Cholesterol LDL cũng có thể được loại bỏ thông qua cơ chế thụ thể LDL không. Một lớp học của các thụ thể bề mặt tế bào, gọi là thụ thể xác thối, tăng LDL biến đổi về mặt hóa học như oxy hóa LDL (hình 32,1), đã được tạo ra bằng cách giải phóng các gốc oxy từ các tế bào nội mô. | 393 32 Overview of Plasma Lipid and Lipoprotein Metabolism hepatic tissues also have abundant LDL receptors. LDL cholesterol can also be removed via non-LDL receptor mechanisms. One class of cell surface receptors termed scavenger receptors takes up chemically modified LDL such as oxidized LDL o Fig. which has been generated by release of oxygen radicals from endothelial cells. Scavenger receptors are not regulated by intracellular cholesterol levels. In peripheral tissues such as macrophages and smooth muscle cells of the arterial wall excess cholesterol accumulates within the plasma membrane and then is transported to the endoplasmic reticulum where it is esteri-fied to cholesteryl esters by the enzyme acyl-CoA cholesterol acyltransferase. It is at this stage that cytoplasmic droplets are formed and that the cells are converted into foam cells an early stage of atherogenesis . Later on cholesteryl esters accumulate as insoluble residues in atherosclerotic plaques. The optimal level of plasma LDL to prevent atherosclerosis and to maintain normal cholesterol homeostasis in humans is not known. At birth the average LDL cholesterol level is 30 mg dL. After birth if the LDL cholesterol level is 100 mg dl LDL is primarily removed through the high affinity LDL receptor pathway. In Western societies the LDL cholesterol is usually 100 mg dl the higher the LDL-cholesterol the greater the amount that is removed by the scavenger pathway. While the exogenous and endogenous pathways are conceptually considered as separate pathways an imbal ance in one often produces an abnormal effect in the other. Thus reduced LPL activity or decreased apo C-II as well as elevated apo C-III or apo C-I can promote hypertriglyceridemia and accumulation of remnant particles from both chylomicrons and VLDL. When the remnant particles are sufficiently small Svedberg flotation units 20 to 60 they can enter the vascular wall and promote atherogenesis. The greater the cholesterol content of
