Endothelial cell secretory granule exocytosis

一层薄薄的连续的细胞覆盖在我们所有血管的内部，将血液与我们的组织和细胞分开。与体内其他细胞不同，血液与健康的内皮细胞接触时不会凝结。这种独特而重要的特性来自于防止血液凝固的分子的分泌，如果血栓形成，这些分子会迅速溶解。然而，内皮细胞并不是只会耍一种把戏；除了控制血液凝固外，它们在调节血液流动、组织修复和生长以及血管和邻近组织的炎症方面也起着至关重要的作用。内皮细胞通过分泌大量不同分子来控制所有这些不同的过程。实际上，血管内皮作为一个高度专业化的多任务分泌机器，对局部环境的变化做出快速反应。内皮细胞正常分泌功能的改变会增加高血压和动脉粥样硬化的风险；中风和心脏病发作的主要原因。我们的研究旨在试图了解调节这些细胞分泌的细胞机制。我们特别关注参与控制血液凝固（血管性血友病因子和组织纤溶酶原激活剂）和炎症（p-选择素和小细胞因子如白介素-8）的肽和蛋白质的分泌。我们结合生物化学、分子、细胞生物学和生物物理学方法，直接分析这些分子在单个内皮细胞中的合成、储存和分泌。了解内皮细胞的分泌功能在正常情况下是如何被控制的，将有助于揭示疾病期间发生的变化，并帮助我们制定治疗血管疾病的新策略

A thin continuous layer of cells covers the inside of all our blood vessels, separating blood from our tissues and cells. Unlike other cells in the body, blood does not clot when in contact with healthy endothelial cells. This unique and vital property stems from the secretion of molecules that prevent blood coagulation, and that rapidly dissolve blood clots if they do form. The endothelium is not however a one-trick-pony; in addition to controlling blood coagulation, they play essential roles in regulating blood flow, tissue repair and growth, and inflammation within the vasculature and adjacent tissues. Endothelial cells control all of these different processes through the secretion of a large number of different molecules. In effect, the vascular endothelium functions as a highly specialised multi-tasking secretory machine that responds rapidly to changes in its local environment. Alterations to the normal secretory function of endothelial cells are though to contribute to an increased risk of hypertension and atherosclerosis; major causes of stroke and heart attacks. Our research is aimed at trying to understanding the cellular mechanisms that regulate secretion from these cells. We focus particularly on the secretion of peptides and proteins involved in the control of blood coagulation (von Willebrand factor and tissue plasminogen activator) and inflammation (p-selectin and small cytokines such as interleukin-8). We combine biochemical, molecular, cell biological and biophysical approaches to directly analyse the synthesis, storage and secretion of these molecules in single endothelial cells. Understanding how the secretory function of endothelial cells is controlled under normal conditions will shed light on the changes that occur during disease and help us to develop new strategies for the treatment of vascular disorders