高级病生第一次课——内皮细胞的病理生理学.ppt

TJ is composed of integral membrane proteins，i.e. junctional adhesion molecules (JAM), occludin, claudin, and cytoplasmic proteins, i.e. zonula occludins-1-3 (ZO1-3) and cingulin. Cytoplasmic proteins then link to actin and myosin light chain (MLC). At AJ, transmembrane molecule vascular endothelial-cadherins (VE-cadherins) form intercellular homodimers at the presence of Ca2+ and connect to actin by β-catenin/α-catenin. Figure legend The endothelial cell as the maestro of thromboregulation. Non-thrombogenic functions shown in green include the thrombomodulin–thrombin protein C system, tissue factor pathway inhibitor, plasmin generating system, and the heparin antithrombin system. Additionally, there are non-thrombogenic interactions with platelets through CD39, nitric oxide, and the eicosanoid pathway. Non-constitutive “activated” functions (red) on the luminal side of the cell include upregulation of cell adhesion molecules and tissue factor, factor IXa binding, platelet activating factor release (PAF), factor V synthesis, and basally: PDGF release and plasminogenactivated inhibitor–1 release. Abluminal matrix deposition of collagen, vWF, fibronectin and thrombospondin are also shown. Regulation of ET-1 synthesis, pathway of ET generation and ET-receptor-mediated actions on smooth muscle cells. Endothelin-1 (ET-1) synthesis is regulated by many factors; stimulators are highlighted in green, and inhibitors are highlighted in red. The product of ET1 transcription is prepro-ET-1, which is cleaved by a neutral endopeptidase to form the active precursor pro-ET-1 or big ET-1. Big ET-1 is converted to the mature peptide by the metalloproteinase endothelin-converting enzyme-1 (ECE-1)1. Two ET receptors have been identified in the vasculature: ET type-A receptors (ETA) reside in vascular smooth muscle cells and mediate vasoconstriction and cell proliferation, whereas ETB receptors reside on endothelial cells and are mainly vasodilatory through NO (which in turn can mediate