The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease.
The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease.
复制标题
DOI：
10.3389/fcvm.2022.820962
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
de Vries MR
中科院分区：
文献类型：
--
作者：
Bezhaeva T;Karper J;Quax PHA;de Vries MR
Toll样受体（TLR）的激活在心血管疾病的发生、发展和结局中起重要作用。复杂TLR介导的信号传导影响血管和心脏功能，包括组织重塑和修复。作为免疫系统的先天性和适应性臂的中心组分，TLR作为模式识别受体与一系列外源性配体和内源性分子或所谓的危险相关分子模式（DAMP）相互作用，所述危险相关分子模式在组织损伤和细胞应激时释放。除了免疫细胞之外，心血管系统内的许多结构细胞，包括内皮细胞、平滑肌细胞、成纤维细胞和心肌细胞表达TLR并且能够释放或感测DAMP。TLR介导的信号级联的局部激活诱导心血管组织修复，但在存在恒定刺激的情况下可能过冲并引起慢性炎症和组织损伤。TLR辅助分子在引导和抑制这些反应朝向充分反应中是必不可少的。此外，辅助分子确保特异性和排他性TLR介导的信号转导的不同细胞和途径参与心血管疾病的发病机制。虽然已经了解了很多关于TLR激活在心血管重塑，TLR辅助分子的确切作用是不完全理解。深入了解TLR辅助分子在心血管系统中的作用，可能为控制心血管疾病的炎症反应开辟新的治疗途径。本综述概述了参与心血管疾病进展的膜TLRs的辅助分子。本文首先综述了TLR信号转导的最新研究进展，重点介绍了在心血管系统中起关键作用的膜TLR及其配体。然后，我们调查目前的证据表明，TLRs辅助分子在血管和心脏重塑，包括心肌梗死，心力衰竭，中风，动脉粥样硬化，静脉移植疾病和动静脉瘘失败的贡献。
Activation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function including tissue remodeling and repair. Being central components of both innate and adaptive arms of the immune system, TLRs interact as pattern recognition receptors with a series of exogenous ligands and endogenous molecules or so-called danger associated molecular patterns (DAMPs) that are released upon tissue injury and cellular stress. Besides immune cells, a number of structural cells within the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts and cardiac myocytes express TLRs and are able to release or sense DAMPs. Local activation of TLR-mediated signaling cascade induces cardiovascular tissue repair but in a presence of constant stimuli can overshoot and cause chronic inflammation and tissue damage. TLR accessory molecules are essential in guiding and dampening these responses toward an adequate reaction. Furthermore, accessory molecules assure specific and exclusive TLR-mediated signal transduction for distinct cells and pathways involved in the pathogenesis of cardiovascular diseases. Although much has been learned about TLRs activation in cardiovascular remodeling, the exact role of TLR accessory molecules is not entirely understood. Deeper understanding of the role of TLR accessory molecules in cardiovascular system may open therapeutic avenues aiming at manipulation of inflammatory response in cardiovascular disease. The present review outlines accessory molecules for membrane TLRs that are involved in cardiovascular disease progression. We first summarize the up-to-date knowledge on TLR signaling focusing on membrane TLRs and their ligands that play a key role in cardiovascular system. We then survey the current evidence of the contribution of TLRs accessory molecules in vascular and cardiac remodeling including myocardial infarction, heart failure, stroke, atherosclerosis, vein graft disease and arterio-venous fistula failure.
影响因子：
4.7
作者：
Cho S;Kim E
通讯作者：
Kim E