Steyers Curtis M, Miller Francis J
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Int J Mol Sci. 2014 Jun 25;15(7):11324-49. doi: 10.3390/ijms150711324.
Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.
慢性炎症性疾病与动脉粥样硬化加速及心血管疾病（CVD）风险增加相关。随着动脉粥样硬化的发病机制越来越被认为是一个炎症过程，动脉粥样硬化与类风湿关节炎、炎症性肠病、狼疮、银屑病、脊柱关节炎等全身性炎症性疾病之间的相似性已成为一个研究热点。内皮功能障碍是动脉粥样硬化起始和维持的关键步骤，可作为未来心血管事件风险的标志物。慢性炎症性疾病患者常于疾病早期即出现内皮功能障碍。因此，在血管内皮水平可能最有助于理解全身性炎症性疾病与动脉粥样硬化之间的关联机制。多种因素，包括循环炎症细胞因子、肿瘤坏死因子-α（TNF-α）、活性氧、氧化型低密度脂蛋白（LDL）、自身抗体及传统危险因素，直接或间接激活内皮细胞，导致血管舒张功能受损、白细胞黏附增加、内皮通透性增加及促血栓形成状态。针对TNF-α介导的炎症的药物制剂可能会降低这些患者发生内皮功能障碍和心血管疾病的风险。了解驱动全身性炎症性疾病患者内皮功能障碍的确切机制可能有助于阐明普通人群中动脉粥样硬化的发病机制。
