Lipid and Non-lipid Factors Affecting Macrophage Dysfunction and Inflammation in Atherosclerosis.
Lipid and Non-lipid Factors Affecting Macrophage Dysfunction and Inflammation in Atherosclerosis.
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DOI：
10.3389/fphys.2018.00654
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发表时间：
2018
影响因子：
4
通讯作者：
Vieira OV
中科院分区：
文献类型：
--
作者：
Gibson MS;Domingues N;Vieira OV
动脉粥样硬化是一种慢性炎症性疾病，是人类死亡的主要原因。病变微环境包含复杂的脂质氧化和细胞因子的积累。浸润的单核细胞响应于这些刺激而极化，导致广谱的巨噬细胞表型。巨噬细胞中脂质负荷的程度影响其表型，从而影响其炎症状态。为了响应过量的致动脉粥样硬化配体，许多正常细胞过程在体内平衡丧失后变得异常。这可能对炎症反应产生直接影响，相反，炎症可能导致细胞功能障碍。在动脉粥样硬化巨噬细胞的溶酶体、内质网和线粒体中存在明确的证据，这是主要的病变细胞类型。此外，一些内在的细胞过程成为失调的条件下阿尔茨海默氏症。旨在恢复疾病条件下的细胞功能的治疗策略是一个持续的令人垂涎的目标。巨噬细胞在促进病变炎症中发挥核心作用，斑块进展和稳定性与巨噬细胞丰度成正比。因此，了解混合物或单个脂质种类如何调节巨噬细胞生物学是动脉粥样硬化研究的一个主要领域。在这篇综述中，我们将讨论如何无数的脂质和脂蛋白类和产品用于模型致动脉粥样硬化，促炎免疫反应促进了更好地了解一些复杂的慢性炎症和细胞功能。尽管如此，脂质氧化会产生复杂的产物混合物，并且没有单一或标准的衍生方法，某些氧化脂质的报告效应存在一些变化。同样，当使用明显相同的脂质配体时，用于体外产生巨噬细胞的方法的差异也可能导致可变的反应。因此，报道的巨噬细胞表型的复杂性对我们理解支持其活化和炎症状态的代谢途径、过程和转变具有意义。使用氧化低密度脂蛋白及其氧化胆固醇酯和磷脂成分刺激巨噬细胞具有巨大的价值，然而现在有一种观点认为，只有与低复杂性脂质物质一起工作才能提供最有用的信息来指导旨在控制动脉粥样硬化和心血管并发症的治疗。
Atherosclerosis is a chronic inflammatory disease and a leading cause of human mortality. The lesional microenvironment contains a complex accumulation of variably oxidized lipids and cytokines. Infiltrating monocytes become polarized in response to these stimuli, resulting in a broad spectrum of macrophage phenotypes. The extent of lipid loading in macrophages influences their phenotype and consequently their inflammatory status. In response to excess atherogenic ligands, many normal cell processes become aberrant following a loss of homeostasis. This can have a direct impact upon the inflammatory response, and conversely inflammation can lead to cell dysfunction. Clear evidence for this exists in the lysosomes, endoplasmic reticulum and mitochondria of atherosclerotic macrophages, the principal lesional cell type. Furthermore, several intrinsic cell processes become dysregulated under lipidotic conditions. Therapeutic strategies aimed at restoring cell function under disease conditions are an ongoing coveted aim. Macrophages play a central role in promoting lesional inflammation, with plaque progression and stability being directly proportional to macrophage abundance. Understanding how mixtures or individual lipid species regulate macrophage biology is therefore a major area of atherosclerosis research. In this review, we will discuss how the myriad of lipid and lipoprotein classes and products used to model atherogenic, proinflammatory immune responses has facilitated a greater understanding of some of the intricacies of chronic inflammation and cell function. Despite this, lipid oxidation produces a complex mixture of products and with no single or standard method of derivatization, there exists some variation in the reported effects of certain oxidized lipids. Likewise, differences in the methods used to generate macrophages in vitro may also lead to variable responses when apparently identical lipid ligands are used. Consequently, the complexity of reported macrophage phenotypes has implications for our understanding of the metabolic pathways, processes and shifts underpinning their activation and inflammatory status. Using oxidized low density lipoproteins and its oxidized cholesteryl esters and phospholipid constituents to stimulate macrophage has been hugely valuable, however there is now an argument that only working with low complexity lipid species can deliver the most useful information to guide therapies aimed at controlling atherosclerosis and cardiovascular complications.
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DOI：
10.1038/nrm4069
发表时间：
2015-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Brar GA;Weissman JS
通讯作者：
Weissman JS
抑制 NLRP3 炎症小体可通过抑制 ox-LDL 摄取和促进胆固醇流出来减弱 THP-1 巨噬细胞泡沫细胞的形成
DOI：
10.1016/j.bbrc.2017.11.025
发表时间：
2018-01-01
影响因子：
3.1
作者：
Chen, Liang;Yao, Qiying;Qu, Peng
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Qu, Peng
影响因子：
6.5
作者：
Cox, Brian E.;Griffin, Evelyn E.;Jerome, W. Gray
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Jerome, W. Gray
影响因子：
64.8
作者：
Bochkov, VN;Kadl, A;Leitinger, N
通讯作者：
Leitinger, N
影响因子：
5.3
作者：
da Silva, Rafaela F.;Lappalainen, Jani;Kovanen, Petri T.
通讯作者：
Kovanen, Petri T.