Vieira-Alves Ildernandes, Coimbra-Campos Leda M C, Sancho Maria, da Silva Rafaela Fernandes, Cortes Steyner F, Lemos Virgínia Soares
Department of Physiology and Biophysics, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Department of Pharmacology, University of Vermont, Burlington, VT, United States.
Front Physiol. 2020 Dec 23;11:621769. doi: 10.3389/fphys.2020.621769. eCollection 2020.
Atherosclerosis constitutes a major risk factor for cardiovascular diseases, the leading cause of morbidity and mortality worldwide. This slowly progressing, chronic inflammatory disorder of large- and medium-sized arteries involves complex recruitment of immune cells, lipid accumulation, and vascular structural remodeling. The α7 nicotinic acetylcholine receptor (α7nAChR) is expressed in several cell types involved in the genesis and progression of atherosclerosis, including macrophages, dendritic cells, T and B cells, vascular endothelial and smooth muscle cells (VSMCs). Recently, the α7nAChR has been described as an essential regulator of inflammation as this receptor mediates the inhibition of cytokine synthesis through the cholinergic anti-inflammatory pathway, a mechanism involved in the attenuation of atherosclerotic disease. Aside from the neuronal cholinergic control of inflammation, the non-neuronal cholinergic system similarly regulates the immune function. Acetylcholine released from T cells acts in an autocrine/paracrine fashion at the α7nAChR of various immune cells to modulate immune function. This mechanism additionally has potential implications in reducing atherosclerotic plaque formation. In contrast, the activation of α7nAChR is linked to the induction of angiogenesis and VSMC proliferation, which may contribute to the progression of atherosclerosis. Therefore, both atheroprotective and pro-atherogenic roles are attributed to the stimulation of α7nAChRs, and their role in the genesis and progression of atheromatous plaque is still under debate. This minireview highlights the current knowledge on the involvement of the α7nAChR in the pathophysiology of atherosclerosis.
动脉粥样硬化是心血管疾病的主要危险因素，而心血管疾病是全球发病和死亡的主要原因。这种在大中型动脉中缓慢进展的慢性炎症性疾病涉及免疫细胞的复杂募集、脂质积累和血管结构重塑。α7烟碱型乙酰胆碱受体（α7nAChR）在参与动脉粥样硬化发生和发展的多种细胞类型中表达，包括巨噬细胞、树突状细胞、T细胞和B细胞、血管内皮细胞和平滑肌细胞（VSMC）。最近，α7nAChR被描述为炎症的重要调节因子，因为该受体通过胆碱能抗炎途径介导细胞因子合成的抑制，这是一种参与减轻动脉粥样硬化疾病的机制。除了神经元对炎症的胆碱能控制外，非神经元胆碱能系统同样调节免疫功能。T细胞释放的乙酰胆碱以自分泌/旁分泌方式作用于各种免疫细胞的α7nAChR，以调节免疫功能。该机制在减少动脉粥样硬化斑块形成方面也具有潜在意义。相反，α7nAChR的激活与血管生成和VSMC增殖的诱导有关，这可能促进动脉粥样硬化的进展。因此，α7nAChRs的刺激既具有抗动脉粥样硬化作用，也具有促动脉粥样硬化作用，它们在动脉粥样斑块发生和发展中的作用仍存在争议。本综述强调了目前关于α7nAChR参与动脉粥样硬化病理生理学的知识。
