Anticoagulant Mechanisms

The formation of thrombin and the deposition of fibrin on the surface of quiescent endothelial cells is impaired by several pathways. The extrinsic tenase activity is inhibited by the Kunitz-type inhibitor, TFPI (Broze et al. 1990 Broze 1995a, b Rapaport 1989) and by the serine protease inhibitor, antithrombin (Rapaport and Rao 1995 van't Veer and Mann 1997). Both inhibitors neutralise factor VIIa only when it is bound to tissue factor. The mature full-length TFPI is a 43-kDa protein with an...

Angiogenic Disorders

After birth, angiogenesis still contributes to organ growth, but during adulthood most blood vessels remain quiescent angiogenesis only occurs in the cycling ovary and placenta during pregnancy. However, endothelial cells (ECs) retain the remarkable ability of dividing rapidly in response to a physiological stimulus, such as hypoxia and inflammation. Angiogenesis is also reactivated during wound healing and repair. In many disorders, however, this stimulus becomes excessive, and the balance...

Von Willebrand Factor

The central role of vWF in haemostasis is supported by several observations. First, vWF is associated with collagen VI in the subendothelium (Rand et al. 1993). Upon de-endothelialisation, subendothelial vWF becomes a potent vascular ligand triggering platelet rolling and tethering. Second, circulating vWF contributes to haemostasis in a dual manner It carries factor VIII and binds to vascular collagens exposed to the blood stream (Bolhuis et al. 1981). Third, it participates in...

References

Alhenc-Gelas F, Tsai SL, Callahan KS, Campbell WB, Johnson AR (1982) Stimulation of prostaglandin formation by vasoactive mediators in cultured human endothelial cells. Prostaglandins 24 723-742 Alonso-Galicia M, Drummond HA, Reddy KK, Falck JR, Roman RJ (1997) Inhibition of 20-HETE production contributes to the vascular responses to nitric oxide. Hypertension 29 320-325 Arai M, Imai H, Metori A, Nakagawa Y (1997) Preferential esterification of endogenously formed 5-hydroxyeicosatetraenoic acid...

Haemodynamics as a Local Risk Factor for Atherogenesis

Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolaemia, hypertension, diabetes and hyperhomocysteinaemia. In the face of these systemic risk factors, certain regions of the arterial vasculature nonetheless remain relatively resistant to the development of atherosclerotic lesions (Gimbrone et al. 2000). There is increasing evidence that the haemodynamically distinct environments in these...

Vascular Permeability and Extracellular Matrix Degradation

Cell Junctions And Extracellular Matrix

Water and nutrients move from blood to tissues across the walls of capillaries and venules. The wall of blood vessels is composed of ECs and mural cells, Fig. 3 Vessel maturation and stabilisation. When vessels sprout, they initially consist of naked endothelial cell channels. These nascent vessels become stabilised by recruitment of smooth muscle cells and pericytes (a process called arteriogenesis), deposition of extracellular matrix and tightening of cell junctions. Blood flow plays a...

Downstream Transcriptional Targets and Functions of KLF2 in Endothelium

Recent work from our laboratory utilising a systems biology approach involving the systematic analyses of large datasets has unveiled KLF2 as a critical integrator of the global transcriptional responses of human endothelial cells to atheroprotective shear stress stimulation. KLF2 overexpression experiments revealed the global programmes downstream of this transcription factor, including blood vessel development, inflammation, thrombosis and vascular tone (Parmar et al. 2005a). Thus, for...

Regulation of KLF2 by Haemodynamic Forces

KLF2 was first shown to be one of a small number of genes upregulated in cultured human endothelial cells exposed to laminar shear stress for 7 days when compared to static (no flow) culture conditions (Dekker et al. 2002). Using in situ hybridisation of adult human arteries, these authors demonstrated that KLF2 expression was restricted to the endothelium within the vessel wall, and that the pattern of expression correlated with predicted types of shear stress. Specifically, endothelial...