Heart Research Institute, Sydney, NSW 2042, Australia.
School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia.
Cells. 2021 Mar 8;10(3):593. doi: 10.3390/cells10030593.
Mural cells collectively refer to the smooth muscle cells and pericytes of the vasculature. This heterogenous population of cells play a crucial role in the regulation of blood pressure, distribution, and the structural integrity of the vascular wall. As such, dysfunction of mural cells can lead to the pathogenesis and progression of a number of diseases pertaining to the vascular system. Cardiovascular diseases, particularly atherosclerosis, are perhaps the most well-described mural cell-centric case. For instance, atherosclerotic plaques are most often described as being composed of a proliferative smooth muscle cap accompanied by a necrotic core. More recently, the role of dysfunctional mural cells in neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, is being recognized. In this review, we begin with an exploration of the mechanisms underlying atherosclerosis and neurodegenerative diseases, such as mural cell plasticity. Next, we highlight a selection of signaling pathways (PDGF, Notch and inflammatory signaling) that are conserved across both diseases. We propose that conserved mural cell signaling mechanisms can be exploited for the identification or development of dual-pronged therapeutics that impart both cardio- and neuroprotective qualities.
壁细胞通常指的是血管的平滑肌细胞和周细胞。这种异质细胞群体在调节血压、分布和血管壁的结构完整性方面起着至关重要的作用。因此,壁细胞功能障碍可导致许多与血管系统相关疾病的发病和进展。心血管疾病,特别是动脉粥样硬化,可能是最典型的以壁细胞为中心的疾病。例如,动脉粥样硬化斑块通常被描述为具有增殖性平滑肌帽,伴有坏死核心。最近,人们认识到功能失调的壁细胞在神经退行性疾病(如阿尔茨海默病和帕金森病)中的作用。在这篇综述中,我们首先探讨了动脉粥样硬化和神经退行性疾病(如壁细胞可塑性)的发病机制。接下来,我们重点介绍了一些信号通路(血小板衍生生长因子、Notch 和炎症信号),这些信号通路在这两种疾病中都有保守存在。我们提出,保守的壁细胞信号机制可以被利用来识别或开发双重作用的治疗药物,既能提供心脏保护又能提供神经保护。