Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, L8:03, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Nat Rev Cardiol. 2015 Apr;12(4):199-211. doi: 10.1038/nrcardio.2015.5. Epub 2015 Feb 10.
The view of atherosclerosis as an inflammatory disease has emerged from observations of immune activation and inflammatory signalling in human atherosclerotic lesions, from the definition of inflammatory biomarkers as independent risk factors for cardiovascular events, and from evidence of low-density lipoprotein-induced immune activation. Studies in animal models of hyperlipidaemia have also supported the beneficial effects of countering inflammation to delay atherosclerosis progression. Specific inflammatory pathways with relevance to human diseases have been identified, and inhibitors of these pathways are either already in use for the treatment of other diseases, or are under development and evaluation. These include 'classic' drugs (such as allopurinol, colchicine, and methotrexate), biologic therapies (for example tumour necrosis factor inhibitors and IL-1 neutralization), as well as targeting of lipid mediators (such as phospholipase inhibitors and antileukotrienes) or intracellular pathways (inhibition of NADPH oxidase, p38 mitogen-activated protein kinase, or phosphodiesterase). The evidence supporting the use of anti-inflammatory therapies for atherosclerosis is mainly based on either observational or small interventional studies evaluating surrogate markers of disease activity. Nevertheless, these data are crucial to understand the role of inflammation in atherosclerosis, and to design randomized controlled studies to evaluate the effect of specific anti-inflammatory strategies on cardiovascular outcomes.
动脉粥样硬化作为一种炎症性疾病的观点，源自于对人类动脉粥样硬化病变中免疫激活和炎症信号的观察，源自于将炎症生物标志物定义为心血管事件的独立风险因素，以及源自于低密度脂蛋白诱导免疫激活的证据。在高脂血症动物模型中的研究也支持了通过对抗炎症来延缓动脉粥样硬化进展的有益效果。与人类疾病相关的特定炎症途径已经被确定，并且这些途径的抑制剂要么已经用于治疗其他疾病，要么正在开发和评估中。这些抑制剂包括“经典”药物（如别嘌醇、秋水仙碱和甲氨蝶呤）、生物疗法（例如肿瘤坏死因子抑制剂和白细胞介素 1 中和），以及针对脂质介质（如磷脂酶抑制剂和抗白三烯）或细胞内途径（抑制 NADPH 氧化酶、p38 丝裂原活化蛋白激酶或磷酸二酯酶）。支持使用抗炎疗法治疗动脉粥样硬化的证据主要基于评估疾病活动替代标志物的观察性或小型干预性研究。然而，这些数据对于理解炎症在动脉粥样硬化中的作用以及设计评估特定抗炎策略对心血管结局的影响的随机对照研究至关重要。
