Regulation of endothelial cell functions by anticoagulant factors and gap junction.

心血管疾病，如动脉粥样硬化和血栓栓塞，是由与致病性凝血和炎症激活相关的内皮功能障碍引起的。我们的目标是了解保护和维持内皮功能的机制。我首先研究了活化蛋白C和血栓调节蛋白对内皮间隙连接的影响。我的结果表明，这些因素增强间隙连接细胞间的通讯。接下来，我指出抑制间隙连接蛋白connexin32会增加组织因子的表达，而过表达connexin32会促进内皮细胞的管状形成。此外，内皮细胞通过间隙连接介导的细胞间相互作用调节单核细胞/中性粒细胞的活化。这些结果表明，活化的蛋白C和血栓调节蛋白调节间隙连接细胞之间的相互作用，以维持内皮功能和体内平衡。

Cardiovascular diseases, such as atherosclerosis and thromboembolism, are caused by endothelial dysfunctions associated with pathogenic activation of blood coagulation and inflammation. Our goal is to understand the mechanisms for protection and maintenance of endothelial functions. I first investigated the effects of activated protein C and thrombomodulin on endothelial gap junction. My results demonstrated that these factors enhance gap junction intercellular communication. Next, I indicated that inhibition of gap junction protein connexin32 increases tissue factor expression and that overexpression connexin32 enhances tube formation of endothelial cells. In addition, endothelial cells modulate monocyte/neutrophil activation via gap junction mediated cell-cell interaction. These results suggested activated protein C and thrombomodulin regulate gap junction cell-cell interaction in order to maintain endothelial functions and homeostasis.