Novel effects of the acyl-coenzyme A:cholesterol acyltransferase inhibitor 58-035 on foam cell development in primary human monocyte-derived macrophages

Novel effects of the acyl-coenzyme A:cholesterol acyltransferase inhibitor 58-035 on foam cell development in primary human monocyte-derived macrophages
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DOI:
10.1161/01.atv.19.9.2199
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发表时间:
1999-09-01
影响因子:
8.7
通讯作者:
Wee, SB
Wee, SB
中科院分区:
医学1区
文献类型:
--
作者:
Rodriguez, A;Bachorik, PS;Wee, SB

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我们研究了酰基辅酶A:胆固醇酰基转移酶(ACAT)抑制剂对泡沫细胞形成过程中原代人类单核细胞来源的巨噬细胞(HMS)中储存的细胞内胆固醇的影响。将HMM暴露于乙酰化低密度脂蛋白(acLDL,500mU/mT蛋白),或不加或不加58-035(1~10mU/m L)或Cl-976(2mU/m L),作用2~48h。在acLDL加ACAT抑制剂孵育的细胞中,总胆固醇(TC)和酯化胆固醇(EC)质量显著降低,而未酯化胆固醇(UC)略有增加。在加入或不加入58-035(2微克/毫升)、高密度脂蛋白(高密度脂蛋白,每毫升400微克蛋白质)或高密度脂蛋白+58-035(每毫升高密度脂蛋白)的情况下,细胞与acLDL(500微克蛋白质/毫升)共孵育48h后,测定细胞的固醇质量。TC和EC分别降低23%和55%(P
We examined the effect of acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors on intracellular cholesterol, stores in primary human monocyte-derived macrophages (HMs) during foam cell formation. HMMs were exposed to acetylated low density lipoprotein (acLDL, 500 mu g protein per mt) with or without 58-035 (1 to 10 mu g/mL) or Cl-976 (2 mu g/mL) for 2 to 48 hours. Total cholesterol (TC) and esterified cholesterol (EC) mass was significantly lower while unesterified cholesterol (UC) increased slightly in cells incubated with acLDL plus ACAT inhibitors. Sterol mass was also measured in cells coincubated with acLDL (500 mu g protein per mt) with or without 58-035 (2 mu g/mL), high density lipoprotein (HDL, 400 mu g protein per mt), or HDL + 58-035 for 48 hours. TC and EC were 23% and 55% lower, respectively (P