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Blood vessels and their constitutive endothelium play a critical role in the maintenance of vascular fluidity, the arrest of hemorrhage (hemostasis), prevention of occlusive vascular phenomena (thrombosis), and regulation of the inflammatory process. The endothelium extends to all recesses of the body and maintains an intimate association with flowing blood and blood cells. However, endothelial cell morphologies, gene-expression profiles, and functions vary among different vascular beds. In straight arterial segments, but not at branch points or curvatures of the arteries or veins, for example, endothelial cells align themselves in parallel to the direction of blood flow. Similarly, endothelial cells in post capillary venules are primarily responsible for mediating adhesion and transmigration of leukocytes, whereas arteriolar endothelium is important for regulation of vasomotor tone. Recent proteomic approaches, moreover, have revealed that endothelial cells have the unique capacity to express and elaborate thromboregulatory molecules which can be classified according to their chronological appearance. Early thromboregulators appear prior to thrombin formation and late thromboregulators arrive after thrombin has formed. This chapter reviews some of the mechanisms that impart thromboresistance to the vascular wall, and discusses their implication for blood vessel health and disease.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: ADAMTS, a disintegrin and metalloproteinase with thrombospondin repeats; ADP, adenosine diphosphate; APC, activated protein C; Apo(a), apolipoprotein(a); ApoE, apolipoprotein E; CD, cluster of differentiation; CD39/ENTPD1, ectonucleotidase triphosphate diphosphohydrolase 1; COX, cyclooxygenase; DDAVP, desmopressin acetate; EPCR, endothelial cell protein C receptor; ET-1, endothelin-1; GP, glycoprotein; HC, homocysteine; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; JAM, junctional adhesion molecule; LFA, lymphocyte function-associated antigen; Lp(a), lipoprotein(a); Mac-1, macrophage-1; MAdCAM-1, mucosal addressin cell adhesion molecule-1; MHC, major histocompatibility complex; NK, natural killer; NO, nitric oxide; NOS, nitric oxide synthase; p11, protein p11, the annexin A2 binding partner; PAF, platelet-activating factor; PAI-1, plasminogen activator inhibitor-1; PECAM, platelet/endothelial cell adhesion molecule; PGI2, prostaglandin I2; PSGL-1, P-selectin glycoprotein ligand-1; TAFI, thrombin-activatable fibrinolysis inhibitor; TF, tissue factor; TM, thrombomodulin; TNF-α, tumor necrosis factor-α; t-PA, tissue-type plasminogen activator; u-PA, urokinase plasminogen activator; uPAR, urokinase receptor; VCAM, vascular cell adhesion molecule; VLA-1, very-late antigen-1; VWF, von Willebrand factor.

The endothelium represents a dynamic interface between flowing blood and the vessel wall, and produces a variety of factors that regulate blood fluidity (Fig. 117–1). Endothelial cells are subject to unique shear stress, to soluble factors in the blood, to signals emanating from the large variety of cells in the circulation, and to cell–cell interactions in the vascular wall, all of which create region-specific phenotypes.1 In addition to modulating vascular permeability and fragility, the endothelium regulates the fluid state of blood by displaying thromboresistance and profibrinolytic potential. All of the above activities serve to maintain patency of all the lumens in the circulation (Fig. 117–1).2

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