Pinsky D J, Yan S F, Lawson C, Naka Y, Chen J X, Connolly E S, Stern D M
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Semin Cell Biol. 1995 Oct;6(5):283-94. doi: 10.1006/scel.1995.0038.
Hypoxia is a common denominator of ischemic microenvironments. Endothelium subjected to oxygen deprivation maintains cell viability and basic biosynthetic mechanisms, but displays multiple changes in properties relevant to vascular homeostasis, including suppression of the anticoagulant cofactor thrombomodulin, decreased barrier function, and generation of proinflammatory cytokines. Diminished intracellular cAMP during the period of hypoxia and lowered nitric oxide/cGMP in the subsequent reperfusion period are proposed as fundamental mechanisms driving vascular dysfunction impacting on coagulation, permeability, vasomotor tone and leukocyte adhesivity. The period of organ preservation for transplantation, recognized to be associated with hypoxia, primes mechanisms leading to subsequent vascular dysfunction which can be ameliorated by buttressing cAMP and nitric oxide/cGMP intra- and intercellular second messenger systems. A mechanism likely to contribute to hypoxia-mediated generation of cytokines, such as interleukin 6, is activation of the transcription factor NF-IL-6, which occurs in oxygen deprivation. These data indicate that study of cellular mechanisms of endothelial perturbation in hypoxia is likely to provide insights ultimately applicable to ischemia-induced vascular damage.
缺氧是缺血性微环境的一个共同特征。处于缺氧状态的内皮细胞维持细胞活力和基本生物合成机制，但在与血管稳态相关的特性方面表现出多种变化，包括抗凝辅因子血栓调节蛋白的抑制、屏障功能降低以及促炎细胞因子的产生。缺氧期间细胞内cAMP减少以及随后再灌注期间一氧化氮/环鸟苷酸降低被认为是驱动血管功能障碍的基本机制，这种功能障碍会影响凝血、通透性、血管舒缩张力和白细胞黏附性。器官移植的保存期被认为与缺氧有关，它引发导致随后血管功能障碍的机制，而通过加强细胞内和细胞间第二信使系统中的cAMP和一氧化氮/环鸟苷酸可以改善这种功能障碍。一种可能导致缺氧介导的细胞因子（如白细胞介素6）产生的机制是转录因子NF-IL-6的激活，这发生在缺氧状态下。这些数据表明，研究缺氧状态下内皮细胞扰动的细胞机制可能会提供最终适用于缺血性血管损伤的见解。
