Macrophages heterogeneity in atherosclerosis - implications for therapy.
Macrophages heterogeneity in atherosclerosis - implications for therapy.
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DOI：
10.1111/j.1582-4934.2010.01121.x
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发表时间：
2010-08
影响因子：
5.3
通讯作者：
Wilson HM
中科院分区：
文献类型：
--
作者：
Wilson HM
动脉粥样硬化是发生在动脉壁内的一种慢性炎症性疾病，是心血管并发症的潜在原因，包括心肌梗死、中风和周围血管疾病。其发病机制涉及多种免疫细胞类型，其中单核细胞/巨噬细胞的作用被广泛接受。胆固醇负载巨噬细胞是斑块的一个特征，在斑块发展的各个阶段都起着重要作用。除了调节脂质代谢外，巨噬细胞还分泌炎症细胞因子、趋化因子和活性氧和活性氮，推动发病机制。它们还会产生蛋白酶和组织因子，导致斑块破裂和血栓形成。然而，巨噬细胞是异质细胞，当被适当激活时，它们吞噬细胞毒性脂蛋白，清除凋亡小体，分泌抗炎细胞因子，合成基质修复蛋白，稳定易损斑块。因此，巨噬细胞活性的药理调节代表了动脉粥样硬化的潜在治疗策略。这篇综述的目的是概述目前对不同巨噬细胞亚群及其单核细胞前体的理解，以及这些亚群对动脉粥样硬化的影响。这将为利用巨噬细胞的异质性作为动脉粥样硬化及其相关疾病的重要诊断和治疗靶点提供新的机会。
Atherosclerosis is a chronic inflammatory disease occurring within the artery wall and is an underlying cause of cardiovascular complications, including myocardial infarction, stroke and peripheral vascular disease. Its pathogenesis involves many immune cell types with a well accepted role for monocyte/macrophages. Cholesterol-loaded macrophages are a characteristic feature of plaques and are major players in all stages of plaque development. As well as modulating lipid metabolism, macrophages secrete inflammatory cytokines, chemokines and reactive oxygen and nitrogen species that drive pathogenesis. They also produce proteases and tissue factor that contribute to plaque rupture and thrombosis. Macrophages are however heterogeneous cells and when appropriately activated, they phagocytose cytotoxic lipoproteins, clear apoptotic bodies, secrete anti-inflammatory cytokines and synthesize matrix repair proteins that stabilize vulnerable plaques. Pharmacological modulation of macrophage activity therefore represents a potential therapeutic strategy for atherosclerosis. The aim of this review is to provide an overview of the current understanding of the different macrophage subsets and their monocyte precursors, and, the implications of these subsets for atherosclerosis. This will present a foundation for highlighting novel opportunities to exploit the heterogeneity of macrophages as important diagnostic and therapeutic targets for atherosclerosis and its associated diseases.
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