Short-term treatment with a 2-carba analog of cyclic phosphatidic acid induces lowering of plasma cholesterol levels
Short-term treatment with a 2-carba analog of cyclic phosphatidic acid induces lowering of plasma cholesterol levels
复制标题
使用环磷脂酸 2-carba 类似物进行短期治疗可降低血浆胆固醇水平
DOI：
10.1016/j.bbrc.2016.03.060
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发表时间：
2016
影响因子：
3.1
通讯作者：
and Kimiko Murakami-Murofushi
中科院分区：
文献类型：
--
作者：
Tamotsu Tsukahara;Hisao Haniu;Yoshikazu Matsuda;and Kimiko Murakami-Murofushi
血浆胆固醇水平与动脉粥样硬化风险增加有关。低密度脂蛋白胆固醇（LDL-C）水平升高是代谢综合征高胆固醇血症的标志。我们之前的研究表明，当乙酰化LDL （AC-LDL）与PPARγ激动剂罗格列酮（ROSI）共同作用时，可以观察到许多油红o阳性巨噬细胞。然而，在rosi刺激的巨噬细胞中添加环磷脂酸（cPA）完全消除油红o染色细胞，表明cPA抑制ppar γ调节的AC-LDL摄取。本研究旨在确定代谢稳定的cPA，以cPA的碳水化合物衍生物（2ccPA）的形式，是否可以降低血浆胆固醇水平，并影响载脂蛋白e敲除（apoE−/−）小鼠动脉粥样硬化相关基因的表达。2ccPA使这些小鼠（n = 3）的LDL-C水平从460降至330 mg/ml，从420降至350 mg/ml，从420降至281 mg/ml。2ccPA还降低了apoe缺陷小鼠高脂肪饮食中脂质代谢相关基因、细胞因子和趋化因子的表达。综上所述，这些结果表明2ccPA控制着apoe缺陷小鼠颈动脉的抗动脉粥样硬化活性。
Plasma cholesterol levels are associated with an increased risk of developing atherosclerosis. An elevated low-density lipoprotein cholesterol (LDL-C) level is a hallmark of hypercholesterolemia in metabolic syndrome. Our previous study suggested that when acetylated LDL (AC-LDL) was co-applied with a PPARγ agonist, rosiglitazone (ROSI), many oil red O-positive macrophages could be observed. However, addition of cyclic phosphatidic acid (cPA) to ROSI-stimulated macrophages completely abolished oil red O-stained cells, indicating that cPA inhibits PPARγ-regulated AC-LDL uptake. This study aimed to determine whether metabolically stabilized cPA, in the form of a carba-derivative of cPA (2ccPA), could reduce plasma cholesterol levels and affect the expression of genes related to atherosclerosis in apolipoprotein E-knockout (apoE−/−) mice. 2ccPA reduced LDL-C levels in these mice (n = 3) from 460 to 330 mg/ml, from 420 to 350 mg/ml, and 420 to 281 mg/ml under a western-type diet. 2ccPA also reduced expression of lipid metabolism-related genes, cytokines, and chemokines in ApoE-deficient mice on a high-fat diet. Taken together, these results suggest that 2ccPA governs anti-atherogenic activities in the carotid arteries of apoE-deficient mice.