Regulation of ACAT in multiple risk factor syndrome

ACAT 在多危险因素综合征中的调节

• 批准号: 14571101
• 负责人: MIYAZAKI Akira
• 金额: $ 2.24万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571101/
• 关键词: ACAT; ACAT2; macrophage; atherosclerosis; foam cell; differentiation; コレステロールエステル

Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) was regarded as a major ACAT isoform expressed in human macrophages. However, the current immunohistochemical studies with an ACAT2 antibody demonstrated significant expression of ACAT2 in macrophage-foam cells in human atherosclerotic lesions. All the macrophages in the lesions expressed ACAT1 while 70-80% of the macrophages expressed ACAT2. Immunoblot and RT-PCR analyses of cultured human monocyte-macrophages demonstrated that immature macrophages expressed only ACAT1 while fully differentiated macrophages expressed both ACAT1 and ACAT2. Additional immunoblot and RT-PCR analyses showed that mouse peritoneal exudate macrophages expressed both ACAT1 and ACAT2 while mouse resident peritoneal macrophages expressed only ACAT1. We conclude that under various pathological conditions, fully differentiated macrophages express ACAT2 in addition to ACAT1.

酰基辅酶A：胆固醇酰基转移酶1 （ACAT1）被认为是在人巨噬细胞中表达的主要ACAT亚型。然而，目前使用ACAT2抗体的免疫组织化学研究表明，ACAT2在人动脉粥样硬化病变的巨噬细胞泡沫细胞中显著表达。病变内巨噬细胞均表达ACAT1, 70-80%的巨噬细胞表达ACAT2。对培养的人单核巨噬细胞的免疫印迹和RT-PCR分析表明，未成熟巨噬细胞仅表达ACAT1，而完全分化的巨噬细胞同时表达ACAT1和ACAT2。免疫印迹和RT-PCR分析显示小鼠腹腔渗出巨噬细胞同时表达ACAT1和ACAT2，而小鼠腹腔巨噬细胞仅表达ACAT1。我们得出结论，在各种病理条件下，完全分化的巨噬细胞除了表达ACAT1外，还表达ACAT2。

项目成果

Kuniyasu, A. et al.: "CD36-mediated endocytic uptake of advanced glycation end products. (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes."Federation of European Biochemical Society Letters. 537. 85-90 (2003)

Kuniyasu, A. 等人：“小鼠 3T3-L1 和人皮下脂肪细胞中 CD36 介导的晚期糖基化终产物 (AGE) 的内吞摄取。”欧洲生化学会快报联合会。

Kuniyasu A, Ohgami N, Hayashi S, Miyazaki A, Horiuchi S, Nakayama H.: "CD36-mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes."Federation of European Biochemical Society Letters. 537. 85-9

Kuniyasu A、Ohgami N、Hayashi S、Miyazaki A、Horiuchi S、Nakayama H.：“CD36 介导的小鼠 3T3-L1 和人皮下脂肪细胞中晚期糖基化终末产物 (AGE) 的内吞摄取。”欧洲生化学会快报联合会

Miyazaki A, Sakai M, Sakamoto Y, Horiuchi S.: "Acyl-coenzyme A: cholesterol acyl transferase inhibitors for controlling hypercholesterolemia and atherosclerosis."Current Opinion in Investigational Drugs. 4. 1095-1099 (2003)

Miyazaki A、Sakai M、Sakamoto Y、Horiuchi S.：“酰基辅酶 A：用于控制高胆固醇血症和动脉粥样硬化的胆固醇酰基转移酶抑制剂。”研究药物的当前观点。

Ohgami, N. et al.: "Advenced glycation end products (AGE) inhbits scavenger receptor class B type I-mediated reverse cholesterol transport : a new cressroad of AGE to cholesterol metabolism."Journal of Atherosclerosis and Thrombosis. 10. 1-6 (2003)

Ohgami, N. 等人：“晚期糖基化终末产物 (AGE) 抑制 B 类清道夫受体 I 型介导的反向胆固醇转运：AGE 与胆固醇代谢的新十字路口。”动脉粥样硬化和血栓形成杂志。

Miyazaki A, Nakayam H, Horiuchi S.: "Scavenger receptors that recognize advanced glycation end products (AGE)."Trends in Cardiovascular Medicine. 12. 258-262 (2002)

Miyazaki A、Nakayam H、Horiuchi S.：“识别晚期糖基化终末产物 (AGE) 的清道夫受体。”心血管医学趋势。