Low density lipoprotein LDL 1 2 1 2 Hisashi MAKINO, Mariko HARADA-SHIBA 1. はじめに Low density lipoprotein LDL 著者連絡先 565-8565 5-7-1 E-mail. mshiba@ncvc.go.jp familial hypercholesterolemia; FH LDL FH LDL 600 1,000 mg/dl 1) 100 1 500 1 LDL proprotein convertase subtilisin/kexin type 9 PCSK9 autosomal recessive hypercholesterolemia adaptor protein autosomal recessive hypercholesterolemia; ARH 3-hydroxy- 3-methyl-glutaryl-CoA HMG-CoA LDL FH LDL LDL-C 400 mg/dl 250 mg/dl LDL LDL LDL B LDL heparininduced extracorporeal precipitation HELP FH peripheral artery disease; PAD LDL FH LDL 2. LDLアフェレシスの方法 1) 単純血漿交換 (plasma exchange) FH 10 2) 二重膜濾過法 (double filtration plasmapheresis) 2 LDL very low density lipoprotein VLDL 2) high density lipoprotein HDL VLDL LDL 10 30 60 197
3)LDL 吸着法 (liposober system) LDL LDL B VLDL LDL Lp a 3) HDL B 150 ml LA15 2 LDL NaCl 5 LA15 LDL LDL ACE 3. LDLアフェレシスの実際 FH LDL 4 6 FH 1 LDL 2 1 LDL 25 kg 10 LDL LDL FH FH LDL FH 図 1 LDL small dense LDL-C LDL 80 small dense LDL-C LDL 4) 4. LDL アフェレシスの抗動脈硬化作用 FH LDL LDL-C intercellular adhesion molecule-1 ICAM-1 endothelial leukocyte adhesion molecule-1 ELAM-1 5) plasminogen activator inhibitor-1 PAI-1 6) LDL LDL 6) NO 7) LDL small dense LDL 図 1 LDL 8) LDL NaCl elution 図 2a mass spectrometry MS MS/MS 198
図 2 LDL proprotein convertase subtilisin/kexin type 9 PCSK9 LDL PCSK9 apolipoprotein C- ApoC- LDL 図 2b Tavori LDL PCSK9 LDL 9) LDL-C 1 LDL LDL PAD LDL LDL-C Ikeya LDL PAD LDL 10) PAD LDL LDL 5. FHにおけるLDLアフェレシスの治療目標と心血管予後への効果 LDL-apheresis atherosclerosis regression study LAARS FH LDL 11) FH LDL 3 20 LDL 5 1 15 1 3 20 3 2 表 1 4) Græsdal 7 10 12) FH LDL 1 / LDL 199
表 1 LDL 4) 1 F 4 19 2 M 6 13 5 12 3 F 9 29 10 27 4 F 6 24 6 10 24 50 5 M 12 27 6 F 22 40 18 7 M 27 29 29 8 F 25 32 31 32 FH 200 mg/dl 6. おわりに 図 3 CABG, coronary artery bypass grafting; MI, myocardial infarction; PTCA, percutaneous transluminal coronary angioplasty. 300 mg/dl 100 mg/dl LDL Hokuriku-FH-LDL- Apheresis Study FH 130 6 LDL percutaneous coronary intervention PCI coronary artery bypass grafting CABG 13) LDL-C 図 3 LDL LDL-C LDL FH PCSK9 14) microsomal triglyceride transfer protein 15) FH LDL-C 1 /1 2 FH LDL LDL LDL-C FH 利益相反の開示 COI 文献 1) Goldstein JL, Brown MS: The Metabolic Basis of Inherited Disease 5 th ed, ed by Yokoyama S, Hayashi R, et al, MacGraw-Hill, New York, 1982 2) Kikkawa T, Yokoyama S, Hayashi R, et al: Specificity of various plasmapheresis techniques for treatment of 200
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