Review Article

PCSK9 和炎症:它们在自身免疫性疾病中的作用,重点是类风湿性关节炎和系统性红斑狼疮

卷 29, 期 6, 2022

发表于: 04 January, 2022

页: [970 - 979] 页: 10

弟呕挨: 10.2174/0929867328666210810150940

价格: $65

Open Access Journals Promotions 2
摘要

尽管自身免疫性疾病和心血管 (CV) 风险之间存在明确的流行病学联系,但病理生理学解释极其复杂且远未阐明。代谢途径失调和慢性低度炎症是常见的途径,但自身免疫性疾病患者的心血管风险仍然被低估。在不同的候选介质中,由于对脂质代谢和炎症反应的综合作用,前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 引起了越来越多的关注。对 PCSK9 抑制剂的研究已经确定了对 CV 结果的明显益处,而对炎症没有确定的影响。相反,来自败血症和 HIV 感染的证据强烈支持 PCSK9 的促炎作用。尽管如此,PCSK9 在自身免疫性疾病中的作用仍不确定。到目前为止,报告的临床发现存在争议,可能反映了对单核细胞/巨噬细胞迁移和激活的 PCSK9 活性知之甚少。围绕 PCSK9 合成和代谢的复杂信号网络也可能发挥作用,尤其是涉及清道夫受体,如 CD36。 PCSK9 信号的这种复杂性在自身免疫疾病模型中似乎特别明显。这也可能解释观察到的血脂谱和 PCSK9 水平之间的独立性,即所谓的“血脂悖论”。在这篇叙述性回顾中,我们将总结当前有关 PCSK9 信号复杂网络的知识。我们将专注于对自身免疫性疾病具有潜在影响的上游和下游途径以及 PCSK9 抑制策略的潜在影响。

关键词: PCSK9、炎症、自身免疫性疾病、类风湿性关节炎、败血症、细胞因子

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