心血管疾病是世界上造成死亡的主要原因之一，而動脈粥狀硬化是潛在的病理機制。動脈粥狀硬化是一種慢性發炎疾病，主要是由於大量的低密度脂蛋白(low-density lipoproteins, LDLs)累積在血管中，而巨噬細胞吞噬LDLs後，會形成泡沫細胞引發不良的免疫反應。因此，巨噬細胞在動脈粥狀硬化中扮演重要的角色，其可再進一步分為M1和M2兩種型態。促進發炎的M1巨噬細胞主要位於斑塊肩部和脂質核心，被認為會使斑塊較不穩定容易破裂並促進血栓形成；相比之下，抗發炎的 M2巨噬細胞大多出現在較穩定的區域，主要會參與動脈粥狀硬化的消退。此外，已知高密度脂蛋白(high-density lipoproteins, HDLs)會透過促進巨噬細胞中膽固醇的排除以及抑制發炎反應和LDLs的氧化來避免動脈粥狀硬化。然而目前較少研究針對HDLs對已分化之M1和M2巨噬細胞的影響。因此在這項研究中，我們想要確定HDLs對M1和M2巨噬細胞是否具有抑制動脈粥狀硬化的能力以及其參與的機制。首先，我們分離人類周邊血液單核細胞並分別分化成M1(LPS+IFN-γ)或M2(IL-4+IL-13)巨噬細胞。M1 巨噬細胞會表現出較細長的形態，並且高表達腫瘤壞死因子α (tumor necrosis factor α, TNF-α)、C-C趨化因子受體7 (C-C motif chemokine receptor 7, CCR7)和C-C趨化因子配體19 (C-C motif chemokine ligand 19, CCL19)。而樹突狀的M2巨噬細胞則是會表達較高的CD206、CCL13、CCL18和精氨酸酶1 (arginase 1, ARG-1)。我們的研究發現，在M1巨噬細胞中，HDLs可透過抑制促進發炎的CCL19及TNF-α表達，並誘導M2標誌物ARG-1表現來發揮抗發炎作用。而在M2巨噬細胞中，HDLs會增加CCR7和CCL18的表達，並且其抗氧化力、膽固醇排出能力和移動能力也都有顯著提升。因此，本研究發現HDLs在M1和M2巨噬細胞中會透過不同機制抑制動脈粥狀硬化。

Cardiovascular disease is the leading cause of death in the world, and atherosclerosis is the underlying mechanism. Atherosclerosis is a chronic inflammatory disease caused by an accumulation of low-density lipoproteins (LDLs) and maladaptive immune responses arising from macrophage-derived foam cells. Macrophages, which play an important role in atherosclerosis, can be further divided into M1- and M2-type. Pro-inflammatory M1 macrophages, predominantly located in plaque shoulder and lipid core, are thought to trigger plaque destabilization and promote thrombosis. In contrast, anti-inflammatory M2 macrophages are found in more stable zones, where these cells are involved in the regression of atherosclerosis. In addition, high-density lipoproteins (HDLs) are known to protect against atherosclerosis by promoting macrophage cholesterol efflux while inhibiting inflammatory responses and LDLs oxidation. In this study, we intend to determine the athero-protective effects of HDLs on M1 and M2 macrophages. First, human peripheral blood mononuclear cells were differentiated into M1 (LPS+IFN-γ) or M2 (IL-4+IL-13) macrophages, respectively. M1 macrophages, which showed elongated morphology, have increased mRNA expression of tumor necrosis factor-α (TNF-α), C-C motif chemokine receptor 7 (CCR7), and C-C motif chemokine ligand 19 (CCL19). While dendritic-like M2 macrophages have the elevation of CD206, CCL13, CCL18, and arginase 1 (ARG-1). HDLs exert anti-inflammatory effects on M1 macrophages by suppressing M1 markers, CCL19 and TNF-α, while inducing M2 marker ARG-1. On the other hand, CCR7 and CCL18 were upregulated in M2 macrophages under HDLs treatment. Additionally, the antioxidant capacity, cholesterol efflux ability, and CCR7-mediated transmigration of M2 macrophages were upregulated by HDLs. Therefore, HDLs indeed exert athero-protective effects on M1 and M2 macrophages via different mechanisms.

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