Department of Mechanical Engineering, Temple University, Philadelphia, PA 19122, USA.
Department of Chemistry, University of Kansas, Lawrence, KS 66045, USA.
Int J Mol Sci. 2021 Jul 21;22(15):7770. doi: 10.3390/ijms22157770.
The endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, excessive leukocyte trafficking, and reactive oxygen species production, leading to organ damage. Therapeutics targeting endothelium inflammation are urgently needed, but strong concerns regarding the level of phenotypic heterogeneity of microvascular endothelial cells between different organs and species have been expressed. Microvascular endothelial cell heterogeneity in different organs and organ-specific variations in endothelial cell structure and function are regulated by intrinsic signals that are differentially expressed across organs and species; a result of this is that neutrophil recruitment to discrete organs may be regulated differently. In this review, we will discuss the morphological and functional variations in differently originated microvascular endothelia and discuss how these variances affect systemic function in response to inflammation. We will review emerging in vivo and in vitro models and techniques, including microphysiological devices, proteomics, and RNA sequencing used to study the cellular and molecular heterogeneity of endothelia from different organs. A better understanding of microvascular endothelial cell heterogeneity will provide a roadmap for developing novel therapeutics to target the endothelium.
内皮细胞是所有血管的内层，它调节止血。它在全身炎症反应的调节中也起着积极的作用。全身炎症性疾病常导致血管内皮屏障功能改变、通透性增加、白细胞过度迁移和活性氧产生，导致器官损伤。急需针对内皮炎症的治疗方法，但人们强烈关注不同器官和物种之间微血管内皮细胞表型异质性的水平。不同器官中微血管内皮细胞的异质性以及内皮细胞结构和功能的器官特异性变化是由内在信号调节的，这些信号在不同器官和物种中表达不同；其结果是，中性粒细胞对离散器官的募集可能受到不同的调节。在这篇综述中，我们将讨论不同来源的微血管内皮细胞的形态和功能变化，并讨论这些差异如何影响炎症反应时的全身功能。我们将回顾新兴的体内和体外模型和技术，包括用于研究不同器官内皮细胞的细胞和分子异质性的微生理设备、蛋白质组学和 RNA 测序。更好地了解微血管内皮细胞的异质性将为开发针对内皮的新型治疗方法提供蓝图。
