Shafeghat Melika, Kazemian Sina, Aminorroaya Arya, Aryan Zahra, Rezaei Nima
Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Chicago, IL, USA.
Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran; Cardiac Primary Prevention Research Center (CPPRC), Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Int Immunopharmacol. 2022 Dec;113(Pt A):109390. doi: 10.1016/j.intimp.2022.109390. Epub 2022 Oct 29.
Cardiovascular disease (CVD) is the major leading cause of morbidity and mortality worldwide. According to the pro-inflammatory nature of CVD, recent studies highlighted the immune system's role in its pathogenesis and development. Toll-like receptors (TLRs) have been identified as dominant innate immune receptors. TLR-7 is an intracellular receptor expressed on endosomes or cytoplasmic reticulum and is responsible for detecting damage-associated molecular patterns, which are remarkable during inflammation and viral infection. In addition to immune cells, TLR-7 is expressed in endothelial cells, vascular smooth muscle cells, and platelets. TLR-7 ligands are single-stranded ribonucleic acid (ssRNA) and short interfering RNA, which can activate the signaling pathway and lead to both inflammatory (e.g., interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor- α (TNF-α)) and anti-inflammatory (e.g., IL-10) cytokines release. By growing evidence, it has been proven that TLR-7 activated platelets can increase the risk of thrombus formation by neutrophil aggregation. At the same time, they have a protective role against thrombosis by releasing granulocyte-macrophage colony-stimulating factors. The same two-sided effect was observed between TLR-7 and atherosclerotic plaque formation. Moreover, recent studies explained an association between TLR-7 activation and increased risk of complete heart block, myocarditis, left ventricular remodeling, and rupture. Here we review the rapid progress that has been made in this field, which has improved our understanding of TLR-7 function in CVDs, and discuss the current treatments targeting this receptor.
心血管疾病（CVD）是全球发病和死亡的主要原因。根据CVD的促炎性质，最近的研究强调了免疫系统在其发病机制和发展中的作用。Toll样受体（TLR）已被确定为主要的天然免疫受体。TLR-7是一种在内体或细胞质内质网上表达的细胞内受体，负责检测损伤相关分子模式，在炎症和病毒感染期间这种模式很显著。除免疫细胞外，TLR-7还在内皮细胞、血管平滑肌细胞和血小板中表达。TLR-7配体是单链核糖核酸（ssRNA）和短干扰RNA，它们可以激活信号通路并导致炎症性细胞因子（如白细胞介素-1（IL-1）、IL-6、IL-12、肿瘤坏死因子-α（TNF-α））和抗炎性细胞因子（如IL-10）的释放。越来越多的证据表明，被激活的TLR-7血小板可通过中性粒细胞聚集增加血栓形成风险。同时，它们通过释放粒细胞-巨噬细胞集落刺激因子对血栓形成具有保护作用。在TLR-7与动脉粥样硬化斑块形成之间也观察到了同样的双向作用。此外，最近的研究解释了TLR-7激活与完全性心脏传导阻滞、心肌炎、左心室重塑和破裂风险增加之间的关联。在此，我们综述了该领域取得的快速进展，这些进展增进了我们对TLR-7在心血管疾病中功能的理解，并讨论了针对该受体的当前治疗方法。
