Endothelial surface

Platelets are the formed elements of the blood which participate in hemostasis. Platelets are enucleated, discoid fragments which arise from mature megakaryocytes in the bone marrow. Under normal circumstances, platelets do not adhere to endothelial surfaces of blood vessels. However, platelets can adhere to damaged areas of blood vessels and become activated in such a way that they can also bind fibrinogen. 

Lynch DR, Guttmann RP (2002) Excitotoxicity perspectives based on N-methyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther 300(3) 717-723 Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995) Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol 37(3) 373-380 Mamdouh Z, Chen X, Kerini LM, Maxfield FR, Muller WA (2003) Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis. Nature 421(6924) 748-753... 

Figure 9.7 Mild anterior uveitis. Collections of macrophages (keratic precipitates) can be seen on the endothelial surface of the cornea (arrowheads).

The structure of the blood capillary wall is complex and varies in different organs and tissues. It consists of a single layer of endothelial cells joined together by intercellular junctions. Each endothelial cell, on an average, is 20-40 pm long, 10-15 pm wide, and 0.1-0.5 pm thick, and contains 10,000-15,000 uniform, spherical vesicles called plasmalemmal vesicles. These vesicles range in size between 60 and 80 nm in diameter. About 70% of these vesicles open on the luminal side of the endothelial surface, and the remaining open within the cytoplasm. Plasmalemmal vesicles are believed to be involved in the pinocytic transport of substances across the endothelium. The transition time of pinocytic vesicles across the cell is... 

LPL found on the endothelial surfaces of the blood capillaries) to produce chylomicron remnants, which are then removed from the circulation by specific remnant receptors located on parenchymal liver cells. VLDLs are secreted by the liver. Following their secretion in blood, VLDLs undergo metabolism in a way... 

A major portion of TFPI is bound to the endothelial surface and can be released from the cells by heparin (28). Platelets contain very small amounts of TFPI, which are released when platelets are activated (29). Figure 6 illustrates the mechanism of inhibition by TFPI. 

The endothelial vascular cells have an important role in maintaining cardiovascular health, producing nitric oxide (NO), a powerful vasodilator. NO also prevents the adhesion of leukocytes and platelets to the endothelial surface and platelet aggregation (Barringer and others 2008 Erdman and others 2007). 

On the neutrophil, the major selectin expressed is L-selectin. This molecule is constitutively expressed on mature neutrophils but may be expressed at low levels (50% of adult) in neonates. Stimulation of endothelial cells with thrombin, histamine, IL-1 and some other agents induces neutrophils (and other leukocytes) to leave the circulation and adhere to the endothelium. They do this by rolling onto the surface of the endothelium, to which they attach via P-selectin translocated from storage sites in Weibel-Palade bodies to the surface of the endothelium upon activation. The expression of P-selectin is short-lived and is replaced on the endothelial surface by E-selectin (whose expression is also regulated by some cytokines), which continues the endothelial-leukocyte interaction. 

ICAM-1 and -2 are constitutively expressed on endothelial cells ICAM-1 may be further up-regulated by exposure to cytokines. ICAM-3 has recently been described (its identity based on the unique specificity of a monoclonal antibody) and is a 124-kDa glycoprotein present on the surfaces of T cells, monocytes and neutrophils its expression may be up-regulated by stimulants such as mitogens. VCAM-1, which is expressed on the luminal surface of cytokine-exposed endothelial cells, binds T cells via VLA-4. It is also expressed on the surface of some leukaemic cell lines, on rheumatoid synovial cells and on some tumours.On the other hand, ICAM-1 is found on all endothelial surfaces, and its interaction with neutrophil integrins is the major mechanism that results in the stimulation of transendothelial migration. 

The Endothelium and Lymphatics The capillary endothelial surface of the lung is the largest in the body [131]. The alveolar-capillary endothelium has... 

The putative role of angiogenesis in chronic inflammatory diseases is the maintenance of the inflammatory state by allowing ongoing recruitment of inflammatory cells and by supplying nutrients and oxygen to proliferating inflamed tissue. The increased endothelial surface creates an enormous capacity for the production of cytokines, adhesion molecules, and other inflammatory stimuli [35]. 

NO also reduces endothelial adhesion of monocytes and leukocytes, key features of the early development of atheromatous plaques. This effect is due to the inhibitory effect of NO on the expression of adhesion molecules on the endothelial surface. In addition, NO may act as an antioxidant, blocking the oxidation of low-density lipoproteins and thus preventing or reducing the formation of foam cells in the vascular wall. Plaque formation is also affected by NO-dependent reduction in endothelial cell permeability to lipoproteins. The importance of eNOS in cardiovascular disease is supported by experiments showing increased atherosclerosis in animals deficient in eNOS by pharmacologic inhibition. Atherosclerosis risk factors, such as smoking, hyperlipidemia, diabetes, and hypertension, are associated with decreased endothelial NO production, and thus enhance atherogenesis. 

Disruption of the endothelial surface of blood vessels expose collagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances liberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phospholipid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Nagy, Z., H. Peters, and I. Huttner. 1981. Endothelial surface charge Blood-brain barrier opening to horseradish peroxidase induced by the polycation protamin sulfate. Acta Neuropathol Suppl (Berl) 7 7. 

LRP is a member of the LDL receptor gene family (ref. 649) and, like the LDL receptor, performs an essential role in the removal of certain lipoprotein particles from the bloodstream. As Heeren et al. (ref. 650) explain, triglycerides are transported mainly by two distinct classes of lipoproteins, the chylomicrons and the very-low-density lipoproteins (VLDL). After assembly in the intestine, chylomicrons are carried via lymph into the bloodstream, where they are transformed at the endothelial surface to remnant lipoproteins through the catalytic action of lipoprotein lipase (for review, see ref. 651,652). After lipolysis, the lipoprotein lipase remains associated with the chylomicron remnants and, in conjunction with apolipoprotein E (apo E) (ref. 653-655), facilitates their clearance by the liver into hepatocytes (ref. 656) via LDL receptors and the LRP (ref. 657-660). (The essential role for both receptors in chylomicron remnant removal in vivo has been demonstrated in gene knockout and gene transfer experiments (ref. 661,662 for review, see ref. 663).)... 

Apart from being a vasodilator, nitric oxide is also a potent inhibitor of neutrophil adhesion to the vascular endothelium. This is due to the inhibitory effect of nitric oxide on the expression of adhesion molecules on the endothelial surface. The role of nitric oxide in protecting the endothelium has been demonstrated by studies that showed that treatment with nitric oxide donors protects against ischemia- and reperfusion-mediated endothelial dysfunction. 

In normal tissues of the vasculature, TFPI is produced by megakaryocytes and the endothelium (102). Once produced, this TFPI is stored in three intravascular pools. These pools are located in the plasma, in platelets, and bound to the endothelium (103). The smallest pool of TFPI is found in the platelets, accounting for less than 2.5% of the intravascular total. This small pool of TFPI is released upon platelet activation (104). 10% to 50% of the intravascular TFPI is in the plasma. Most plasma-based TFPI is bound to plasma lipoproteins (104,105). Approximately 5% of the plasma pool of TFPI circulates in the free form (103,104,105). The lipoprotein-bound TFPI is reported to be of relatively low inhibitory activity (104). The largest pool of TFPI is found bound to the endothelial surface (103,104,106). This pool can account for 50% to 90% of the total intravascular TFPI,... 

Formation of thrombus at the site of endothelial damage. Von Willebrand factor exposed at sites of endothelial damage acts to bind platelets to the vessel wall. Tissue factor, expressed on subendothelial tissue and cytokine-primed macrophages, acts to generate thrombin, which activates platelets and produces fibrin. TFPI, normally present on the endothelial surface, can be released by heparins and can inhibit tissue factor-induced thrombin generation. Abbreviations ADP adenosine disphosphate TFP1, tissue factor pathway inhibitor. 

Figure 3 Electrostatic sorting and gating of molecules by the endothelial surface.

---