The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1β monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies.

中文翻译：

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动脉粥样硬化心血管疾病及其他疾病的内皮功能障碍：从机制到药物治疗

内皮是血管壁内衬的细胞单层，在维持多器官健康和体内平衡方面起着关键作用。健康的内皮功能包括动态维持血管张力、血管生成、止血以及提供抗氧化、抗炎和抗血栓形成界面。血管内皮功能障碍表现为内皮依赖性血管舒张受损、氧化应激加剧、慢性炎症、白细胞粘附和渗透性过高以及内皮细胞衰老。最近的研究表明，内皮细胞代谢和内皮间质转化的改变是内皮功能障碍的新特征。内皮功能障碍被认为是多种人类全血管疾病的标志，包括动脉粥样硬化、高血压和糖尿病。β单克隆抗体可对抗内皮功能障碍，作为其临床益处的一部分。非编码 RNA 对内皮功能障碍的调节为这些新描述的内皮功能障碍调节因子提供了新的见解，从而产生了潜在的新治疗方法。总之，更好地了解内皮细胞的多种（功能障碍）功能不仅会加深我们对人类疾病的理解，还会加速有效的治疗药物的发现。在这篇综述中，我们及时概述了内皮功能的多个层次，描述了内皮功能障碍的后果和机制，并确定了有效靶向治疗的途径。