アポBの変性によるLDLと細胞の関係

• Published in: 動脈硬化 Vol. 18; no. 3; pp. 237 - 243
• Main Authors: 坂田 信裕, 中村 治雄
• Format: Journal Article
• Language: English
• Published: Japan Atherosclerosis Society 1990
• ISSN: 0386-2682

Recently, investigation of cell foaming in atherosclerosis suggested that macrophages have alternative mechanism for taking up LDL distinct from the LDL receptor. The pathway of macrophages recognizes modified LDL (e.g., acetylated LDL) and is so-called "scavenger pathway". In this report we summarized the mechanism of modification of apoprotein B in LDL and difference of metabolism of LDL and modified LDL by LDL receptor pathway and scavenger pathway, respectively, based on our experiments and other reports.Various types of modified LDL include chemical modification, complex or aggregation and cellular modification. Acetylation of LDL by acetic anhydride is known to remove positive charges from lysine residue of apoprotein B100. This modification of LDL produces lipoprotein particles that can cause cholesterol-loaded formation in macrophage in vitro. Although mechanism of LDL modification is not yet well cleared in vivo, several reports suggested relation with oxidation by cell. Also oxidized LDL has more negative charge than native LDL and is metabolized by macrophages.Modification of apoprotein B in LDL and metabolism of the lipoprotein by scavenger pathway in macrophages could be very important mechanism for cell foaming in atherosclerotic lesion.The following study is also conducted in relation between calcium antagonist and metabolism of modified LDL.Calcium channel blockers were suggested that may be effective in preventing the atherosclerosis in cholesterol-fed animals. Therefore, we examined effects of calcium antagonist, diltiazem, on metabolism of modified LDL in macrophages.Our data indicated that uptakes of acetylated LDL by macrophages were increased by diltiazem 1×10-4M. However, cellular cholesterol content did not change when the cell incubated with acetylated LDL and with or without diltiazem 1×10-4M. On cholesterol efflux by HDL3 from macrophages, diltiazem 1×10-4M decreased cellular total cholesterol content compared with HDL3 alone.These result suggested that diltiazem might enhance uptake of modified LDL and efflux of cellular cholesterol in macrophages.