Institut National de la Santé et de la Recherche Médicale, Paris Cardiovascular Research Center, France.
Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):887-93. doi: 10.1161/ATVBAHA.111.224873. Epub 2012 Feb 9.
Apoptotic cell death is an important feature of atherosclerotic plaques, and it seems to exert both beneficial and detrimental effects depending on the cell type and plaque stage. Because late apoptotic cells can launch proatherogenic inflammatory responses, adequate engulfment of apoptotic cells (efferocytosis) by macrophages is important to withstand atherosclerosis progression. Several efferocytosis systems, composed of different phagocytic receptors, apoptotic ligands, and bridging molecules, can be distinguished. Because phagocytes in atherosclerotic plaques are very much solicited, a fully operative efferocytosis system seems to be an absolute requisite. Indeed, recent studies demonstrate that deletion of just 1 of the efferocytosis pathways aggravates atherosclerosis. This review discusses the role of apoptosis in atherosclerosis and general mechanisms of efferocytosis, to end with indirect and direct indications of the significance of effective efferocytosis in atherosclerosis.
细胞凋亡是动脉粥样硬化斑块的一个重要特征,它似乎具有双重作用,具体取决于细胞类型和斑块阶段。由于晚期凋亡细胞可引发促动脉粥样硬化的炎症反应,因此巨噬细胞充分吞噬凋亡细胞(凋亡细胞清除)对于抵抗动脉粥样硬化进展非常重要。可以区分几种由不同吞噬受体、凋亡配体和桥接分子组成的凋亡细胞清除系统。由于动脉粥样硬化斑块中的吞噬细胞受到强烈刺激,因此一个功能完备的凋亡细胞清除系统似乎是绝对必要的。事实上,最近的研究表明,仅删除凋亡细胞清除途径之一就会加重动脉粥样硬化。本文讨论了细胞凋亡在动脉粥样硬化中的作用以及凋亡细胞清除的一般机制,最后讨论了有效凋亡细胞清除在动脉粥样硬化中的间接和直接意义。