title: Vascular endothelial cell activation and permeability responses to thrombin.
abstract: The serine protease, thrombin, evokes numerous endothelial cell responses which regulate hemostasis, thrombosis and vessel wall pathophysiology. One such response, the development of intercellular gap formation and vascular permeability is relevant to each of these processes and is a cardinal features of inflammation. Regulation of endothelial cell gap formation and therefore permeability is a function of a dynamic balance between competing adhesive, barrier-promoting tethering forces and contractile, tension-producing forces which result in barrier dysfunction. The key tethering events governing focal endothelial cell adhesion to the extracellular matrix and cell-cell interactions are poorly understood. In contrast, information is rapidly increasing regarding endothelial-specific contractile processes driven by the actomyosin molecular motor. The level of myosin light chain phosphorylation catalyzed by a unique myosin light chain kinase promotes productive actin-myosin interaction and governs the degree of centripetal tension produced. In this review the signal transducing and contractile mechanisms by which thrombin elicits endothelial cellular activation through its specific receptor are addressed. The pathways by which thrombin may alter the balance between contractile and tethering forces to promote endothelial cell gap formation are discussed.
authors.affiliation: Department of Physiology, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Garcia
authors.forename: F M
authors.initials: FM
authors.lastname: Pavalko
authors.forename: C E
authors.initials: CE
authors.lastname: Patterson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects*; D002448:Cell Adhesion; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D010740:Phospholipases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D011494:Protein Kinases; D010740:Phospholipases; D013917:Thrombin; D002118:Calcium