Division of Cardiovascular Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA, USA.
Cardiovasc Res. 2021 Nov 22;117(13):2525-2536. doi: 10.1093/cvr/cvab303.
Inflammation orchestrates each stage of the life cycle of atherosclerotic plaques. Indeed, inflammatory mediators likely link many traditional and emerging risk factors with atherogenesis. Atheroma initiation involves endothelial activation with recruitment of leucocytes to the arterial intima, where they interact with lipoproteins or their derivatives that have accumulated in this layer. The prolonged and usually clinically silent progression of atherosclerosis involves periods of smouldering inflammation, punctuated by episodes of acute activation that may arise from inflammatory mediators released from sites of extravascular injury or infection or from subclinical disruptions of the plaque. Smooth muscle cells and infiltrating leucocytes can proliferate but also undergo various forms of cell death that typically lead to formation of a lipid-rich 'necrotic' core within the evolving intimal lesion. Extracellular matrix synthesized by smooth muscle cells can form a fibrous cap that overlies the lesion's core. Thus, during progression of atheroma, cells not only procreate but perish. Inflammatory mediators participate in both processes. The ultimate clinical complication of atherosclerotic plaques involves disruption that provokes thrombosis, either by fracture of the plaque's fibrous cap or superficial erosion. The consequent clots can cause acute ischaemic syndromes if they embarrass perfusion. Incorporation of the thrombi can promote plaque healing and progressive intimal thickening that can aggravate stenosis and further limit downstream blood flow. Inflammatory mediators regulate many aspects of both plaque disruption and healing process. Thus, inflammatory processes contribute to all phases of the life cycle of atherosclerotic plaques, and represent ripe targets for mitigating the disease.
炎症在动脉粥样硬化斑块的生命周期的每个阶段都起着协调作用。事实上，炎症介质可能将许多传统和新兴的风险因素与动脉粥样硬化的发生联系起来。动脉粥样硬化的起始涉及内皮细胞的激活，导致白细胞募集到动脉内膜，在那里它们与脂蛋白或其在该层中积累的衍生物相互作用。动脉粥样硬化的长期且通常是无症状的进展涉及到炎症的潜伏期，由急性激活期打断，这些急性激活期可能是由血管外损伤或感染部位释放的炎症介质或斑块的亚临床破坏引起的。平滑肌细胞和浸润的白细胞可以增殖，但也会经历各种形式的细胞死亡，这些细胞死亡通常会导致在不断发展的内膜病变内形成富含脂质的“坏死”核心。平滑肌细胞合成的细胞外基质可以形成覆盖病变核心的纤维帽。因此，在动脉粥样硬化斑块的进展过程中，细胞不仅繁殖而且死亡。炎症介质参与这两个过程。动脉粥样硬化斑块的最终临床并发症涉及到斑块破裂引发的血栓形成，这可能是由于斑块的纤维帽断裂或表面侵蚀引起的。由此产生的血栓如果妨碍灌注，则会导致急性缺血综合征。血栓的形成可以促进斑块的愈合和内膜的进行性增厚，这会加重狭窄并进一步限制下游血流。炎症介质调节斑块破裂和愈合过程的许多方面。因此，炎症过程参与动脉粥样硬化斑块生命周期的所有阶段，是减轻疾病的成熟靶点。
