Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus
Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus
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DOI：
10.1016/j.jaut.2022.102863
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发表时间：
2022-10-01
影响因子：
12.8
通讯作者：
Ji, Fusui
中科院分区：
文献类型：
--
作者：
Liu, Yudong;Yu, Xue;Ji, Fusui
系统性红斑狼疮(SLE)与心血管疾病(CVD)的风险相关，心血管疾病会显著增加疾病的死亡率和发病率。与系统性红斑狼疮早期动脉粥样硬化和心血管疾病发展相关的总体机制尚不清楚，但已被认为是严重的免疫失调和传统的心血管危险因素之间复杂相互作用的结果。系统性红斑狼疮患者异常的全身性炎症可能导致血脂异常和功能障碍，从而进一步加剧动脉粥样硬化的形成。内皮损伤和血管修复/血管生成之间的强烈失衡的存在促进了血管损伤，这是动脉粥样硬化性心血管疾病进展的早期步骤。以I型干扰素负荷过大、巨噬细胞、血小板和补体激活、中性粒细胞失调和中性粒细胞胞外陷阱形成、T细胞激活失控、自身抗体产生过多和免疫复合体形成为特征的严重的先天和获得性免疫失调是导致SLE加速CVD的主要原因。虽然设计靶向疗法来纠正免疫激活失调在治疗SLE相关心血管疾病方面可能是有益的，但还需要更多的工作来确定如何将这些发现转化为临床实践。此外，一些生物标记物在改善系统性红斑狼疮心血管疾病风险分层方面显示出诊断潜力，进一步的前瞻性研究将有助于了解哪一个生物标记物(S)在评估与系统性红斑狼疮相关的心血管疾病方面最有影响力(S)。为了改善系统性红斑狼疮的心血管疾病预后，迫切需要继续努力确定新的机制，建立评估心血管疾病风险的标准，并预测心血管疾病的进展。
Systemic lupus erythematosus (SLE) is associated with a significant risk of cardiovascular disease (CVD), which substantially increases disease mortality and morbidity. The overall mechanisms associated with the develop-ment of premature atherosclerosis and CVD in SLE remain unclear, but has been considered as a result of an intricate interplay between the profound immune dysregulation and traditional CVD risk factors. Aberrant systemic inflammation in SLE may lead to an abnormal lipid profile and dysfunction, which can further fuel the pro-atherosclerotic environment. The existence of a strong imbalance between endothelial damage and vascular repair/angiogenesis promotes vascular injury, which is the early step in the progression of atherosclerotic CVD. Profound innate and adaptive immune dysregulation, characterized by excessive type I interferon burden, aberrant macrophage, platelet and complements activation, neutrophil dysregulation and neutrophil extracel-lular traps formation, uncontrolled T cell activation, and excessive autoantibody production and immune complex formation, have been proposed to promote accelerated CVD in SLE. While designing targeted therapies to correct the dysregulated immune activation may be beneficial in the treatment of SLE-related CVD, much additional work is needed to determine how to translate these findings into clinical practice. Additionally, a number of biomarkers display diagnostic potentials in improving CVD risk stratification in SLE, further pro-spective studies will help understand which biomarker(s) will be the most impactful one(s) in assessing SLE-linked CVD. Continued efforts to identify novel mechanisms and to establish criteria for assessing CVD risk as well as predicting CVD progression are in great need to improve CVD outcomes in SLE.