Supplementary Material for: Lysophosphatidylcholine Acyltransferase-3 Expression Is Associated with Atherosclerosis Progression

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.

游离花生四烯酸（free arachidonic acid, AA）是白三烯、前列腺素等脂质介质的重要前体，可诱导炎症反应，并与动脉粥样硬化进展密切相关。现有研究证实，溶血磷脂酰胆碱酰基转移酶3（lysophosphatidylcholine acyltransferase-3, LPCAT3）可将溶血磷脂酰胆碱（lysophosphatidylcholine, LPC）与游离AA转化为携带花生四烯酸的磷脂酰胆碱（arachidonyl-PC），从而调控细胞内游离AA的水平。然而，LPCAT3与动脉粥样硬化之间的关联仍有待阐明。本研究通过成像质谱法分析人类与小鼠的动脉粥样硬化组织，以深入探究涉及LPCAT3的花生四烯酰基磷脂酰胆碱代谢过程。研究数据显示，花生四烯酰基磷脂酰胆碱与LPC在人类动脉粥样硬化组织中呈互补分布：随着动脉粥样硬化进展，花生四烯酰基磷脂酰胆碱水平逐渐降低，而LPC水平逐步升高。此外，研究发现LPCAT3的表达与花生四烯酰基磷脂酰胆碱的分布随动脉粥样硬化进展呈现同源性变化。与之相对，在载脂蛋白E缺陷型小鼠中，动脉粥样硬化的发生同时伴随着花生四烯酰基磷脂酰胆碱积累与LPCAT3表达上调。综上，本研究结果提示，LPCAT3的表达调控或许与人类动脉粥样硬化进展存在关联。