Blood vessels, especially their endothelial lining, play a critical role in the maintenance of vascular fluidity, arrest of hemorrhage (hemostasis), prevention of occlusive vascular phenomena (thrombosis), and regulation of inflammatory cell processes. 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. For example, in straight arterial segments, but not at branch points or curvatures of the arteries or veins, endothelial cells align themselves in parallel to the direction of blood flow. Similarly, endothelial cells in postcapillary venules are primarily responsible for mediating adhesion and transmigration of leukocytes, whereas arteriolar endothelium is important for regulation of vasomotor tone. Proteomic studies have revealed that endothelial cells have the unique capacity to express and elaborate thromboregulatory molecules, which can be classified according to their chronologic appearance after vascular injury. Early thromboregulators appear before thrombin formation, and late thromboregulators arrive after thrombin has formed. This chapter reviews some of the mechanisms by which the vascular wall regulates hemostasis and discusses their implications for vascular health and disease (Table 114–1).
Acronyms and Abbreviations
APC, activated protein C; Apo, apolipoprotein; APS, antiphospholipid syndrome; C5a, complement factor 5a; CAM, cell adhesion molecule; COX, cyclooxygenase; DAG, diacylglycerol; DDAVP, deamino D-arginine vasopressin; EPCR, endothelial protein C receptor; GMP, guanosine monophosphate; IL, interleukin; IP3, inositol triphosphate; Lp(a), lipoprotein(a); NFκB, nuclear factor kappa B; NO, nitric oxide; NOS, nitric oxide synthase; PAF, platelet-activating factor; PDGF, platelet-derived growth factor; PECAM, platelet endothelial cell adhesion molecule; PGI2, prostacyclin; PGIS, prostacyclin synthase; PSGL, P-selectin glycoprotein ligand; scu-PA, single-chain urokinase-type plasminogen activator; TAFI, thrombin-activatable fibrinolysis inhibitor; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; TNF, tumor necrosis factor; t-PA, tissue-type plasminogen activator; VWF, von Willebrand factor.
TABLE 114–1.Chronology of Endothelial Cell Thromboregulators ||Download (.pdf) TABLE 114–1. Chronology of Endothelial Cell Thromboregulators
Nitric oxide (NO)
Eicosanoids (prostacyclin and prostaglandin D2)
Endothelial cell CD39/ENTPDase1
Endothelial cell/heparin proteoglycans
Tissue factor pathway inhibitor
Fibrinolytic system (plasminogen activators, inhibitors, and receptors)
Thrombomodulin–protein C–protein S pathway
Cellular adhesion molecules
VASCULAR FUNCTION IN HEMOSTASIS: INTRODUCTION
The endothelium represents a dynamic interface between flowing blood and the vessel wall and produces a variety of factors that regulate blood fluidity (Fig. 114–1). Endothelial cells are subject to unique shear stress forces, to soluble factors in the blood, and to signals emanating from cells in the circulation, vascular wall, and tissues, all of which create region-specific phenotypes.1–3 In addition to modulating vascular permeability and fragility, the endothelium regulates the fluid state of blood through its thromboresistant nature, profibrinolytic properties, and antiinflammatory potential. These activities maintain vascular patency.4