Castellino F J, Ploplis V A
W. M. Keck Center for Transgene Research, and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1(0 1):140-5. doi: 10.1111/j.1538-7836.2009.03410.x.
Alterations in expression of protein C (PC) pathway components have been identified in patients with active inflammatory disease states. While the PC pathway plays a pivotal role in regulating coagulation and fibrinolysis, activated PC (aPC) also exhibits cytoprotective properties. For example, PC-deficient mice challenged in septic/endotoxemic models exhibit phenotypes that include hypotension, disseminated intravascular coagulation, elevated inflammatory mediators, neutrophil adhesion to the microvascular endothelium, and loss of protective endothelial and epithelial cell barriers. Further, inflammatory bowel disease has been correlated with diminished endothelial PC receptor and thrombomodulin levels in the intestinal mucosa. Downregulated expression of the cofactor, protein S, as well as PC, is also associated with ischemic stroke. Studies to elucidate further the structural elements that differentiate the various functions of PC will serve to identify novel therapeutic approaches toward regulating these and other diseases.
在患有活动性炎症疾病的患者中，已发现蛋白C（PC）途径成分的表达发生改变。虽然PC途径在调节凝血和纤维蛋白溶解中起关键作用，但活化蛋白C（aPC）也具有细胞保护特性。例如，在脓毒症/内毒素血症模型中受到挑战的PC缺陷小鼠表现出包括低血压、弥散性血管内凝血、炎症介质升高、中性粒细胞粘附于微血管内皮以及保护性内皮和上皮细胞屏障丧失等表型。此外，炎症性肠病与肠黏膜中内皮PC受体和血栓调节蛋白水平降低相关。辅因子蛋白S以及PC的表达下调也与缺血性中风有关。进一步阐明区分PC各种功能的结构元件的研究将有助于确定调节这些疾病和其他疾病的新治疗方法。
