Update on lipids, inflammation and atherothrombosis
Update on lipids, inflammation and atherothrombosis
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DOI：
10.1160/ths10-11-0717
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发表时间：
2011-06-01
影响因子：
6.7
通讯作者：
Vilahur, Gemma
中科院分区：
文献类型：
--
作者：
Badimon, Lina;Storey, Robert F.;Vilahur, Gemma
动脉粥样硬化是一种累及动脉壁的炎性疾病，其特征是脂质在血管壁中进行性积聚。第一步是脂质（LDL）在内膜中的内化，内皮活化增强内皮层的渗透性以及细胞因子/趋化因子和粘附分子的表达。这些事件增加了LDL颗粒在细胞外基质中的积累，在细胞外基质中它们聚集/融合，被蛋白聚糖保留，并成为氧化和酶促修饰的靶标。反过来，保留的促动脉粥样硬化LDL增强选择性白细胞募集和附着到内皮层，诱导它们穿过内皮进入内膜。虽然平滑肌细胞数量随着斑块进展的严重程度而下降，但单核细胞分化为巨噬细胞，这是一个与模式识别受体（包括清道夫受体和Toll样受体）上调相关的过程，导致泡沫细胞形成。泡沫细胞释放生长因子、细胞因子、金属蛋白酶和活性氧，所有这些都延续和放大血管重塑过程。此外，巨噬细胞释放组织因子，一旦斑块破裂，有助于血栓形成。暴露于侵蚀性病变中的平滑肌细胞也能够通过LRP-1受体内化LDL，获得促血栓形成表型并释放组织因子。血小板识别破裂或侵蚀的动脉粥样硬化斑块中的配体，启动血小板活化和聚集，导致血栓形成和动脉粥样硬化血栓形成疾病的临床表现。此外，血小板有助于局部炎症反应，也可能参与祖细胞募集。
Atherosclerosis is an inflammatory disease that involves the arterial wall and is characterised by the progressive accumulation of lipids in the vessel wall. The first step is the internalisation of lipids (LDL) in the intima with endothelial activation which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. These events increase LDL particles accumulation in the extracellular matrix where they aggregate/fuse, are retained by proteoglycans and become targets for oxidative and enzymatic modifications. In turn, retained pro-atherogenic LDLs enhance selective leukocyte recruitment and attachment to the endothelial layer inducing their transmigration across the endothelium into the intima. While smooth muscle cell numbers decline with the severity of plaque progression, monocytes differentiate into macrophages, a process associated with the upregulation of pattern recognition receptors including scavenger receptors and Toll-like receptors leading to foam cell formation. Foam cells release growth factors, cytokines, metalloproteinases and reactive oxygen species all of which perpetuate and amplify the vascular remodelling process. In addition, macrophages release tissue factor that, upon plaque rupture, contributes to thrombus formation. Smooth muscle cells exposed in eroded lesions are also able to internalise LDL through LRP-1 receptors acquiring a pro-thrombotic phenotype and releasing tissue factor. Platelets recognise ligands in the ruptured or eroded atherosclerotic plaque, initiate platelet activation and aggregation leading to thrombosis and to the clinical manifestation of the atherothrombotic disease. Additionally, platelets contribute to the local inflammatory response and may also participate in progenitor cell recruitment.