Crosstalk Between Macrophages and Vascular Smooth Muscle Cells in Atherosclerotic Plaque Stability.
Crosstalk Between Macrophages and Vascular Smooth Muscle Cells in Atherosclerotic Plaque Stability.
复制标题
动脉粥样硬化斑块稳定性中巨噬细胞和血管平滑肌细胞之间的串扰。
DOI：
10.1161/atvbaha.121.316233
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Yurdagul A Jr
中科院分区：
文献类型：
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作者：
Yurdagul A Jr
大多数急性心血管事件是由于斑块破裂引起的，含有大坏死核和薄纤维帽的动脉粥样硬化斑块更容易破裂，而具有小坏死核和厚纤维帽的病变更容易破裂。动脉粥样硬化斑块由各种细胞外基质蛋白、修饰的脂蛋白颗粒和不同来源的细胞（即血管细胞和白细胞）组成。尽管关于导致斑块不稳定的机制已经被揭示很多，但几个关键领域仍然不完全清楚。本焦点综述重点介绍了与细胞串扰相关的过程以及组织微环境在确定细胞功能和斑块稳定性中的作用。最近的进展强调了动脉粥样硬化斑块脆弱性的关键基础，特别是巨噬细胞清除死亡细胞和血管平滑肌细胞表型转换的能力受损。然而，这些过程并不是孤立发生的，因为巨噬细胞和血管平滑肌细胞之间的串扰以及与其周围微环境的相互作用在决定斑块稳定性方面发挥着重要作用。了解动脉粥样硬化斑块内细胞串扰的这些方面可能有助于了解如何改变细胞行为，并确定将易破裂的动脉粥样硬化斑块转化为稳定病变的新方法。稳定和不稳定动脉粥样硬化的特征。稳定斑块的特征是厚的纤维帽和小的坏死核。这些斑块还显示出 vSMC 静止的特征并且具有低 MMP 活性。稳定斑块中的巨噬细胞也表现出完整的胞吞作用。易破裂的斑块含有大的坏死核心和薄的纤维帽。这些动脉粥样硬化斑块还表现出与 vSMC 去分化相关的特征，并含有高 MMP 活性和 ECM 蛋白水解作用。来自易于破裂的动脉粥样硬化斑块的巨噬细胞也表现出胞吞作用受损。动脉粥样硬化斑块的稳定性归因于溶解介质和炎症因子之间的平衡，使得溶解介质的增加导致斑块更稳定，而炎症因子的增加则促进斑块更脆弱。
Most acute cardiovascular events are due to plaque rupture, with atheromas containing large necrotic cores and thin fibrous caps being more susceptible to rupture and lesions with small necrotic cores and thick fibrous caps being more protected from rupture. Atherosclerotic plaques are comprised of various extracellular matrix proteins, modified lipoprotein particles, and cells of different origins, i.e. vascular cells and leukocytes. Although much has been revealed about the mechanisms that lead to plaque instability, several key areas remain incompletely understood. This In-Focus Review highlights processes related to cellular crosstalk and the role of the tissue microenvironment in determining cell function and plaque stability. Recent advances highlight critical underpinnings of atherosclerotic plaque vulnerability, particularly impairments in the ability of macrophages to clear dead cells and phenotypic switching of vascular smooth muscle cells. However, these processes do not occur in isolation, as crosstalk between macrophages and vascular smooth muscle cells and interactions with their surrounding microenvironment play a significant role in determining plaque stability. Understanding these aspects of cellular crosstalk within an atherosclerotic plaque may shed light on how to modify cell behavior and identify novel approaches to transform rupture-prone atheromas into stable lesions. Features of Stable and Unstable Atherosclerosis. Stable plaques are characterized by a thick fibrous cap and small necrotic core. These plaques also show features of vSMC quiescence and have low MMP activity. Macrophages in stable plaques also show intact efferocytosis. Rupture-prone plaques contain large necrotic cores and thin fibrous caps. These atheromas also show features associated with vSMC de-differentiation and contain high MMP activity and ECM proteolysis. Macrophages from rupture-prone atheromas also display impaired efferocytosis. The stability of an atherosclerotic plaque is owed to a balance between resolving mediators and inflammatory factors such that an increase in resolution mediators drive a more stable plaque, whereas an increase in inflammatory factors promote a more vulnerable plaque.