Abstract：
Cardiovascular diseases (CVDs) linked to atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is primarily caused by the accumulation of oxidized forms of low density lipoprotein (LDL) in macrophages (MΦs) in the subendothelial layer of arteries leading to foam cell and fatty streak formation. Many studies suggest that LDL that is modified by myeloperoxidase (MPO) is a key player in the development of atherosclerosis. MΦs can adopt a variety of functional phenotypes that include mainly the proinflammatory M1 and the anti-inflammatory M2 MΦ phenotypes which are both implicated in the process of atherogenesis. In fact, MΦs that reside in atherosclerostic lesions were shown to express a variety of phenotypes ranging between the M1- and M2 MΦ types. Recently, we pointed out the involvement of MPO oxidized-LDL (Mox-LDL) in increasing inflammation in MΦs by reducing their secretion of IL-10. Since little is known about Mox-LDL-mediated pro-atherosclerostic responses in MΦs, our study aimed at analyzing the in vitro effects of Mox-LDL at this level through making use of the well-established model of human THP-1-derived Mφs. Our results demonstrate that Mox-LDL has no effect on apoptosis, reactive oxygen species (ROS) generation and cell death in our cell model; yet, interestingly, our results show that Mox-LDL is significantly engulfed at a higher rate in the different MΦ subtypes supporting its key role in foam cell formation during the progression of the disease as well as previous data that were generated using another primary MΦ cell model of atherosclerosis.
摘要：
与动脉粥样硬化相关的心血管疾病（CVD）仍然是全球死亡的主要原因。动脉粥样硬化主要是由巨噬细胞（MΦ）中氧化形式的低密度脂蛋白（LDL）在动脉内皮下层的积累引起的，导致泡沫细胞和脂肪条纹的形成。许多研究表明，髓过氧化物酶（MPO）修饰的LDL是动脉粥样硬化发展的关键参与者。MΦ可以采用多种功能表型，主要包括促炎M1和抗炎M2MΦ表型，这两种表型都与动脉粥样硬化过程有关。事实上,显示存在于动脉粥样硬化病变中的MΦ表达M1-和M2MΦ类型之间的多种表型。最近,我们指出MPO氧化LDL（Mox-LDL）通过减少其IL-10的分泌而增加MΦ的炎症。由于对MΦ中Mox-LDL介导的前动脉粥样硬化反应知之甚少，我们的研究旨在通过利用已建立的人THP-1衍生的Mφs模型来分析Mox-LDL在该水平上的体外作用。我们的结果表明，Mox-LDL对细胞凋亡没有影响，在我们的细胞模型中，活性氧（ROS）的产生和细胞死亡；然而，有趣的是,我们的结果表明,Mox-LDL在不同的MΦ亚型中以更高的速率被显著吞噬,这支持了其在疾病进展期间泡沫细胞形成中的关键作用,以及使用另一种原发性动脉粥样硬化MΦ细胞模型产生的先前数据.
