Department of Bioengineering, Lehigh University, Bethlehem, PA, United States.
Department of Physiology and Renal Research Institute, New York Medical College at the Touro University, Valhalla, NY, United States.
Matrix Biol. 2018 Oct;71-72:421-431. doi: 10.1016/j.matbio.2018.01.026. Epub 2018 Feb 1.
Dysfunctional endothelial cells are an essential contributor to the progression of diverse chronic cardiovascular, renal, and metabolic diseases. It manifests in impairment of nitric oxide-dependent vasorelaxation, vascular permeability, and leukocytes deterrent. While endothelial glycocalyx is known to regulate these functions, glycocalyx has been shown to be impaired in pathologic settings leading to endothelial dysfunction. Are these findings coincidental or are they indicative of a potential cooperation of the glycocalyx and the endothelium in inducing a dysfunctional phenotype? The main thrust of this overview is to advance a hypothesis on the existence of vicious circle relations between impaired endothelial glycocalyx and endothelial cell dysfunction. We briefly introduce physiology and pathology of blood flow-induced components of mechanotransduction in endothelial cells, as this function is dependent on glycocalyx and is critically involved in the development of endothelial dysfunction. Next, we present a series of experimental findings and arguments favoring the view on the impairment of mechanotransduction in dysfunctional endothelia. We advance the concept of feedback reinforcement between perturbed endothelial glycocalyx and progression of endothelial dysfunction and sketch therapeutic approaches to restore them. Among those we introduce our recently designed liposomal nanocarriers of preassembled glycocalyx and present evidence of their ability to expeditiously restore endothelial mechanotransduction.
功能失调的内皮细胞是多种慢性心血管、肾脏和代谢疾病进展的重要因素。它表现为一氧化氮依赖的血管舒张、血管通透性和白细胞抑制受损。虽然已知内皮糖萼调节这些功能，但在导致内皮功能障碍的病理情况下，糖萼已被证明受损。这些发现是偶然的，还是表明糖萼和内皮之间存在潜在的合作，导致功能失调表型？本文的主要目的是提出一个假说，即受损的内皮糖萼和内皮细胞功能障碍之间存在恶性循环关系。我们简要介绍血流诱导的内皮细胞机械转导成分的生理学和病理学，因为该功能依赖于糖萼，并严重参与内皮功能障碍的发展。接下来，我们提出了一系列支持功能失调内皮细胞中机械转导受损的实验发现和论点。我们提出了内皮糖萼紊乱和内皮功能障碍进展之间的反馈强化概念，并概述了恢复它们的治疗方法。其中，我们介绍了我们最近设计的预先组装的糖萼的脂质体纳米载体，并提出了它们能够迅速恢复内皮机械转导的证据。
