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溶血磷脂酰胆碱酰基转移酶-3表达与动脉粥样硬化进展相关。

Lysophosphatidylcholine Acyltransferase-3 Expression Is Associated with Atherosclerosis Progression.

作者信息

Tanaka Hiroki, Zaima Nobuhiro, Sasaki Takeshi, Yamamoto Naoto, Inuzuka Kazunori, Yata Tatsuro, Iwaki Takayuki, Umemura Kazuo, Sano Hideto, Suzuki Yuko, Urano Tetsumei, Setou Mitsutoshi, Unno Naoki

机构信息

Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

J Vasc Res. 2017;54(4):200-208. doi: 10.1159/000473879. Epub 2017 Jul 6.

Abstract

Free arachidonic acid (AA) is an important precursor of lipid mediators such as leukotrienes and prostaglandins that induces inflammation and is associated with atherosclerosis progression. Recent studies have shown that lysophosphatidylcholine acyltransferase-3 (LPCAT3) converts lysophosphatidylcholine (LPC) and free AA into phosphatidylcholine (PC)-containing AA (arachidonyl-PC) and thereby can regulate intracellular free-AA levels. However, the association between LPCAT3 and atherosclerosis remains to be established. In this study, we analyzed human and mouse atherosclerotic tissues to gain insight into the arachidonyl-PC metabolism involving LPCAT3 using imaging mass spectrometry. The data revealed a complementary distribution of arachidonyl-PC and LPC in human atherosclerotic tissues with arachidonyl-PC decreasing and LPC increasing as atherosclerosis progressed. Furthermore, we found a homologous distribution of LPCAT3 expression and arachidonyl-PC based on atherosclerotic progression. In contrast, in ApoE-deficient mice, atherosclerosis increased both arachidonyl-PC accumulation and LPCAT3 expression. Taken together, these findings suggest that the regulation of LPCAT3 expression might be associated with atherosclerotic progression in humans.

摘要

游离花生四烯酸(AA)是脂质介质(如白三烯和前列腺素)的重要前体,可诱导炎症并与动脉粥样硬化进展相关。最近的研究表明,溶血磷脂酰胆碱酰基转移酶-3(LPCAT3)可将溶血磷脂酰胆碱(LPC)和游离AA转化为含花生四烯酸的磷脂酰胆碱(花生四烯酰-PC),从而调节细胞内游离AA水平。然而,LPCAT3与动脉粥样硬化之间的关联仍有待确定。在本研究中,我们分析了人类和小鼠的动脉粥样硬化组织,以利用成像质谱法深入了解涉及LPCAT3的花生四烯酰-PC代谢。数据显示,在人类动脉粥样硬化组织中,花生四烯酰-PC和LPC呈互补分布,随着动脉粥样硬化进展,花生四烯酰-PC减少而LPC增加。此外,基于动脉粥样硬化进展,我们发现LPCAT3表达与花生四烯酰-PC呈同源分布。相比之下,在载脂蛋白E缺乏的小鼠中,动脉粥样硬化增加了花生四烯酰-PC的积累和LPCAT3的表达。综上所述,这些发现表明LPCAT3表达的调节可能与人类动脉粥样硬化进展相关。

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