The role of Wnt signalling in development of coronary artery disease and its risk factors.
The role of Wnt signalling in development of coronary artery disease and its risk factors.
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DOI：
10.1098/rsob.200128
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发表时间：
2020-10
期刊：
影响因子：
5.8
通讯作者：
Mani A
中科院分区：
文献类型：
--
作者：
Liu Y;Neogi A;Mani A
Wnt信号通路由高度保守的级联事件组成，这些事件控制细胞分化、凋亡和细胞定向。Wnt信号转导途径主要有三种：经典Wnt信号转导途径（或Wnt/β-catenin信号转导途径）、非经典平面细胞极性信号转导途径和非经典Wnt/Ca 2+信号转导途径。Wnt信号通路的改变与多种疾病有关，如骨密度紊乱、不同的恶性肿瘤、心脏畸形和心力衰竭。冠心病是美国最常见的心脏病类型。动脉粥样硬化是一个多步骤的病理过程，其开始于脂质沉积和内皮细胞功能障碍，引发炎症反应，随后是单核细胞的募集和聚集。随后，单核细胞分化为组织驻留的巨噬细胞，并通过摄取修饰的低密度脂蛋白转化为泡沫细胞。同时，内膜下脂质进一步积聚，血管平滑肌细胞浸润和增殖，细胞外基质沉积。最终形成动脉粥样硬化斑块或内膜和中膜增生，导致管腔狭窄和心肌血流减少，导致胸痛、心绞痛甚至心肌梗死。Wnt通路参与该过程的所有不同阶段，从内皮功能障碍到脂质存款，以及从初始炎症到斑块形成。本文从临床和实验两个方面探讨了Wnt级联在冠心病发病中的作用。
The Wnt signalling pathways are composed of a highly conserved cascade of events that govern cell differentiation, apoptosis and cell orientation. Three major and distinct Wnt signalling pathways have been characterized: the canonical Wnt pathway (or Wnt/β-catenin pathway), the non-canonical planar cell polarity pathway and the non-canonical Wnt/Ca2+ pathway. Altered Wnt signalling pathway has been associated with diverse diseases such as disorders of bone density, different malignancies, cardiac malformations and heart failure. Coronary artery disease is the most common type of heart disease in the United States. Atherosclerosis is a multi-step pathological process, which starts with lipid deposition and endothelial cell dysfunction, triggering inflammatory reactions, followed by recruitment and aggregation of monocytes. Subsequently, monocytes differentiate into tissue-resident macrophages and transform into foam cells by the uptake of modified low-density lipoprotein. Meanwhile, further accumulations of lipids, infiltration and proliferation of vascular smooth muscle cells, and deposition of the extracellular matrix occur under the intima. An atheromatous plaque or hyperplasia of the intima and media is eventually formed, resulting in luminal narrowing and reduced blood flow to the myocardium, leading to chest pain, angina and even myocardial infarction. The Wnt pathway participates in all different stages of this process, from endothelial dysfunction to lipid deposit, and from initial inflammation to plaque formation. Here, we focus on the role of Wnt cascade in pathophysiological mechanisms that take part in coronary artery disease from both clinical and experimental perspectives.
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