Phenotypic modulation of macrophages in response to plaque lipids.
Phenotypic modulation of macrophages in response to plaque lipids.
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DOI：
10.1097/mol.0b013e32834a97e4
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发表时间：
2011-10
影响因子：
4.4
通讯作者：
Leitinger N
中科院分区：
文献类型：
--
作者：
Adamson S;Leitinger N
巨噬细胞在血管壁中的积聚是动脉粥样硬化的标志。动脉粥样硬化斑块巨噬细胞的生物学特性决定了病变的大小、组成和稳定性。在动脉粥样硬化斑块中，巨噬细胞遇到由多种脂质氧化产物组成的微环境，每种脂质氧化产物具有不同的生物学效应。在这篇综述中，我们总结了最近的进展，我们了解斑块脂质对巨噬细胞表型极化的影响。小鼠和人类的动脉粥样硬化病变包含各种巨噬细胞表型，它们在介导炎症、清除死细胞和可能的消退中发挥不同的作用。巨噬细胞通过上调特定基因组来改变其表型和生物学功能以响应斑块脂质。氧化脂质与模式识别受体的相互作用以及胆固醇晶体对炎性小体的激活驱动巨噬细胞向炎性M1表型发展。当氧化磷脂通过Nrf 2激活应激反应基因时，会产生一种新的表型Mox。其他脂质介质如亚硝基化脂肪酸和ω-3脂肪酸衍生产物使斑块巨噬细胞趋向抗炎和促消退表型。更深入地了解脂质在动脉粥样硬化斑块中的积累如何影响巨噬细胞的表型和功能，从而影响动脉粥样硬化病变的发展和稳定性，将有助于设计新的干预策略。
The accumulation of macrophages in the vascular wall is a hallmark of atherosclerosis. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition and stability. In atherosclerotic plaques, macrophages encounter a microenvironment that is comprised of a variety of lipid oxidation products, each of which has diverse biological effects. In this review, we summarize recent advances in our understanding of the effects of plaque lipids on macrophage phenotypic polarization. Atherosclerotic lesions in mice and in humans contain various macrophage phenotypes, which play different roles in mediating inflammation, the clearance of dead cells, and possibly resolution. Macrophages alter their phenotype and biological function in response to plaque lipids through the upregulation of specific sets of genes. Interaction of oxidized lipids with pattern recognition receptors and activation of the inflammasome by cholesterol crystals drive macrophages towards an inflammatory M1 phenotype. A new phenotype, Mox, develops when oxidized phospholipids activate stress response genes via Nrf2. Other lipid mediators such as nitrosylated-fatty acids and omega-3 fatty acid-derived products polarize plaque macrophages towards anti-inflammatory and proresolving phenotypes. A deeper understanding of how lipids that accumulate in atherosclerotic plaques affect macrophage phenotype and function and thus atherosclerotic lesion development and stability will help to devise novel strategies for intervention.