Low density lipoprotein（LDL）アフェレシス

Size: px

Start display at page:

Download "Low density lipoprotein（LDL）アフェレシス"

りさこくぬぎ
7 years ago
Views:

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.

1 Low density lipoprotein LDL Hisashi MAKINO, Mariko HARADA-SHIBA 1. はじめに Low density lipoprotein LDL 著者連絡先 [email protected] familial hypercholesterolemia; FH LDL FH LDL 600 1,000 mg/dl 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

2 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

3 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 表 1 4) Græsdal ) 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.

4 表 1 LDL 4) 1 F M F F M F M F 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 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, ) Kikkawa T, Yokoyama S, Hayashi R, et al: Specificity of various plasmapheresis techniques for treatment of 200

5 hypercholesterolemia. Current Practice in Therapeutic Plasmapheresis (International Congress Series, No 694), ed by Shiokawa Y, Inoue N, Excerpta Medica, Amsterdam, 1985, ) Yokoyama S, Hayashi R, Kikkawa T, et al: Specific sorbent of apolipoprotein B-containing lipoproteins for plasmapheresis. Characterization and experimental use in hypercholesterolemic rabbits. Arteriosclerosis 4: ,1984 4) Makino H, Harada-Shiba M: Long-term effect of low-density lipoprotein apheresis in patients with homozygous familial hypercholesterolemia. Ther Apher Dial 7: , ) Sampietro T, Tuoni M, Ferdeghini M, et al: Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia. Circulation 96: , ) Kobayashi S, Oka M, Moriya H, et al: LDL-apheresis reduces P-Selectin, CRP and fibrinogen -- possible important implications for improving atherosclerosis. Ther Apher Dial 10: , ) Tamai O, Matsuoka H, Itabe H, et al: Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation 95:76-82, ) Yuasa Y, Osaki T, Makino H, et al: Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis. Ther Apher Dial 18: , ) Tavori H, Giunzioni I, Linton MF, et al: Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis. Circ Res 113: , ) Tsurumi-Ikeya Y, Tamura K, Azuma K, et al: Sustained inhibition of oxidized low-density lipoprotein is involved in the long-term therapeutic effects of apheresis in dialysis patients. Arterioscler Thromb Vasc Biol 30: , ) Kroon AA, Aengevaeren WR, van der Werf T, et al: LDL- Apheresis Atherosclerosis Regression Study (LAARS). Effect of aggressive versus conventional lipid lowering treatment on coronary atherosclerosis. Circulation 93: , ) Græsdal A, Bogsrud MP, Holven KB, et al: Apheresis in homozygous familial hypercholesterolemia: the results of a follow-up of all Norwegian patients with homozygous familial hypercholesterolemia. J Clin Lipidol 6: 331-9, ) Mabuchi H, Koizumi J, Shimizu M, et al: Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL- Apheresis Study Group. Am J Cardiol 82: , ) Roth EM, McKenney JM, Hanotin C, et al: Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 367: , ) Cuchel M, Meagher EA, du Toit Theron H, et al: Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet 381: 40-6,

C/NC : committed/noncommitted

C/NC : committed/noncommitted 110 time post-icd implant 1) The Cardiac Arrhythmia Suppression Trial (CAST) Investigators Preliminary report : Effect of encainaide and flecainide on mortality in a