臨床検査51巻5号

2007年05月発行

今月の主題 脂質 脂質代謝異常と疾病

低HDLコレステロールと疾病

著者： 河村彰¹ 朔啓二郎¹

所属機関： ¹福岡大学医学部内科学第二

ページ範囲：P.507 - P.513

　低HDLコレステロール(HDL-C)血症が動脈硬化の危険因子として認識されるようになって久しいが，HDLの代謝経路の解明が進んできたのは比較的最近のことである．高LDL-C血症に対する心臓病一次予防，二次予防の大規模臨床研究が多数行われてきたのに対し，低HDL-C血症に対する予後や治療効果をみた臨床研究は少ない．また，低HDL-C血症だけを認める場合に治療の対象になるか，HDL-Cは増加すべきか否かなどは，いまだ議論が多い．本稿では，HDLによる動脈硬化防御の分子機構，低HDL-C血症の成因およびその治療法，治療効果について概説する．〔臨床検査　51：507-513，2007〕

参考文献

1) Stamler J, Wentworth D, Neaton JD：Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356, 222 primary screenees of the Multiple Risk Factor Intervention Trial(MRFIT). JAMA 256：2823-2828, 1986

2) Matsuzaki M, Kita T, Mabuchi H, et al：Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia. Circ J 66：1087-1095, 2002

3) Matsuzaki M, Kita T, Mabuchi H, et al：Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease：secondary prevention cohort study of the Japan Lipid Intervention Trial(J-LIT). Circ J 66：1096-1100, 2002

4) 日本動脈硬化学会(編)：動脈硬化性疾患診療ガイドライン2002年版，2002

5) Zhang B, Saku K, Ohta T：In vivo metabolism of HDL, apo A-I, and lp A-I, and function of HDL--a clinical perspective. J Atheroscler Thromb 7：59-66, 2000

6) Chan DC, Barrett PH, Watts GF：Recent studies of lipoprotein kinetics in the metabolic syndrome and related disorders. Curr Opin Lipidol 17：28-36, 2006

7) Marcil M, Brooks-Wilson A, Clee SM, et al：Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux. Lancet 354：1341-1346, 1999

8) Bodzioch M, Orso E, Klucken J, et al：The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat Genet 22：347-351, 1999

9) Rust S, Rosier M, Funke H, et al：Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet 22：352-355, 1999

10) Saku K, Zhang B, Shirai K, et al：Hyperinsulinemic hypoalphalipoproteinemia as a new indicator for coronary heart disease. J Am Coll Cardiol 34：1443-1451, 1999

11) Staels B, Dallongeville J, Auwerx J, et al：Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98：2088-2093, 1998

12) Fruchart JC, Duriez P, Staels B：Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol 10：245-257, 1999

13) Chinetti G, Gbaguidi FG, Griglio S, et al：CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 101：2411-2417, 2000

14) Hirano K, Yamashita S, Nakagawa Y, et al：Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions. Circ Res 85：108-116, 1999

15) Jian B, de la Llera-Moya M, Ji Y, et al：Scavenger receptor class B type I as a mediator of cellular cholesterol efflux to lipoproteins and phospholipid acceptors. J Biol Chem 273：5599-5606, 1998

16) Jin FY, Kamanna VS, Kashyap ML：Niacin decreases removal of high-density lipoprotein apolipoprotein A-I but not cholesterol ester by Hep G2 cells. Implication for reverse cholesterol transport. Arterioscler Thromb Vasc Biol 17：2020-2028, 1997

17) Martin G, Duez H, Blanquart C, et al：Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I. J Clin Invest 107：1423-1432, 2001

18) Schaefer JR, Schweer H, Ikewaki K, et al：Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease. Atherosclerosis 144：177-184, 1999

19) Le Goff W, Guerin M, Chapman MJ：Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia. Pharmacol Ther 101：17-38, 2004

20) Jones P, Kafonek S, Laurora I, et al：Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia(the CURVES study). Am J Cardiol 81：582-587, 1998. Erratum in：Am J Cardiol 82：128, 1998

21) Ballantyne CM, Herd JA, Ferlic LL, et al：Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation 99：736-743, 1999