Oram J F
University of Washington, Division of Metabolism, Endocrinology and Nutrition, Box 356426, Seattle, WA 98195-6426, USA.
Biochim Biophys Acta. 2000 Dec 15;1529(1-3):321-30. doi: 10.1016/s1388-1981(00)00157-8.
Tangier disease is an autosomal recessive genetic disorder characterized by a severe high-density lipoprotein (HDL) deficiency, sterol deposition in tissue macrophages, and prevalent atherosclerosis. Mutations in the ATP binding cassette transporter ABCA1 cause Tangier disease and other familial HDL deficiencies. ABCA1 controls a cellular pathway that secretes cholesterol and phospholipids to lipid-poor apolipoproteins. This implies that an inability of newly synthesized apolipoproteins to acquire cellular lipids by the ABCA1 pathway leads to their rapid degradation and an over-accumulation of cholesterol in macrophages. Thus, ABCA1 plays a critical role in modulating flux of tissue cholesterol and phospholipids into the reverse cholesterol transport pathway, making it an important therapeutic target for clearing excess cholesterol from macrophages and preventing atherosclerosis.
丹吉尔病是一种常染色体隐性遗传病，其特征为严重的高密度脂蛋白（HDL）缺乏、组织巨噬细胞中甾醇沉积以及普遍存在的动脉粥样硬化。ATP结合盒转运体ABCA1的突变会导致丹吉尔病和其他家族性HDL缺乏症。ABCA1控制着一条细胞途径，该途径将胆固醇和磷脂分泌到脂质含量低的载脂蛋白中。这意味着新合成的载脂蛋白无法通过ABCA1途径获取细胞脂质会导致其快速降解以及巨噬细胞中胆固醇的过度积累。因此，ABCA1在调节组织胆固醇和磷脂进入胆固醇逆向转运途径的通量方面起着关键作用，使其成为从巨噬细胞中清除多余胆固醇并预防动脉粥样硬化的重要治疗靶点。
