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疾病中的血管通透性

Vascular Permeability in Diseases.

机构信息

Faculté de Médecine, Université Denis Diderot Paris, 75013 Paris, France.

出版信息

Int J Mol Sci. 2022 Mar 26;23(7):3645. doi: 10.3390/ijms23073645.

Abstract

Vascular permeability is a selective mechanism that maintains the exchange between vessels, tissues, and organs. The regulation was mostly studied during the nineteenth century by physiologists who defined physical laws and equations, taking blood, tissue interstitial, and oncotic pressure into account. During the last decades, a better knowledge of vascular cell functions and blood-vessel interactions opens a new area of vascular biology. Endothelial cell receptors vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule (ICAM), vascular endothelial growth factor receptor (VEGFR-2), receptor for advanced glycation end products (RAGE), and mediators were identified and their role in homeostasis and pathological situations was described. The molecular differences of endothelial cell junctions (tight, gap, and adherens junctions) and their role in vascular permeability were characterized in different organs. The main mediators of vasomotricity and permeability, such as prostaglandins, nitric oxide (NO), prostacyclin, vascular growth factor (VEGF), and cytokines, have been demonstrated to possess major functions in steady state and pathological situations. Leukocytes were shown to adhere to endothelium and migrate during inflammatory situations and infectious diseases. Increased vascular permeability is linked to endothelium integrity. Glycocalyx, when intact, may limit cancer cell metastasis. Biological modifications of blood and tissue constituents occurring in diabetes mellitus were responsible for increased permeability and, consequently, ocular and renal complications. Vascular pressure and fluidity are major determinants of pulmonary and cerebral edema. Beside the treatment of the infectious disease, of the blood circulation dysfunction and inflammatory condition, drugs (cyclooxygenase inhibitors) and specific antibodies anti-cytokine (anti-VEGF) have been demonstrated to reduce the severity and the mortality in diseases that exhibited enhanced vascular permeability.

摘要

血管通透性是一种选择性机制,可维持血管、组织和器官之间的物质交换。这种调节功能主要在 19 世纪被生理学家研究,他们定义了物理定律和方程,考虑了血液、组织间质和胶体渗透压。在过去几十年中,对血管细胞功能和血管相互作用的进一步了解为血管生物学开辟了一个新领域。内皮细胞受体(血管细胞黏附分子 [VCAM]、细胞间黏附分子 [ICAM]、血管内皮生长因子受体 [VEGFR-2]、晚期糖基化终产物受体 [RAGE] 和介质)被鉴定出来,其在稳态和病理情况下的作用也被描述。不同器官中内皮细胞连接(紧密连接、缝隙连接和黏附连接)的分子差异及其在血管通透性中的作用也得到了表征。血管舒缩和通透性的主要介质,如前列腺素、一氧化氮(NO)、前列环素、血管生长因子(VEGF)和细胞因子,被证明在稳态和病理情况下具有重要作用。白细胞在炎症和感染性疾病期间被证明可黏附于内皮细胞并迁移。血管通透性增加与内皮细胞完整性有关。当糖萼完整时,它可能会限制癌细胞转移。糖尿病患者血液和组织成分的生物学改变可导致通透性增加,从而导致眼部和肾脏并发症。血管压力和流动性是肺和脑水肿的主要决定因素。除了治疗传染病、血液循环功能障碍和炎症状况外,还证明药物(环氧化酶抑制剂)和针对特定细胞因子的抗体(抗 VEGF)可降低血管通透性增强相关疾病的严重程度和死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00e9/8998843/12d3dd7104df/ijms-23-03645-g001.jpg

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