Endothelial cells Endothelium

Three years later Robert F Furchgott discov ered that the relaxing of smooth muscles such as blood vessel walls was stimulated by an unknown substance produced in the lining of the blood vessels (the endothelium) He called this substance the endothelium-dependent relaxing factor or EDRF and in 1986 showed that EDRF was NO Louis J Ignarro reached the same conclusion at about the same time Further support was provided by Salvador Moncada who showed that endothelial cells did in deed produce NO and that the l arginine to l citrulline conversion was responsible... 

Vasodilating molecule(s) liberated from vascular endothelial cells in response to chemical substances (i.e., Acetylcholine, bradykinin, substance P, etc.) or mechanical stimuli (i.e., shear stress, transmural pressure, etc.). The EDRF includes NO, prostaglandin J2 (prostacyclin), and endothelium-derived hypeipolarizing factor (EDHF). 

The vascular endothelium plays an important role in regulation of vascular tone and permeability. Dilatation of arterioles to increase blood flow and constriction of endothelial cells of postcapillary venules causing exsudation of plasma constituents illustrates the complex nature of this cell type. Moreover, by expression of adhesion molecules and secretion of chemokines endothelial cells play an important role in the recruitment of leukocytes to the inflamed area. Endothelial cells express two basic types of adhesion molecules on their surface ... 

Furchgott and Zawadzki [1] first discovered that endothelial cells release a substance(s) responsible for the relaxation of vascular smooth muscle by acetylcholine this substance was named endothelium-derived relaxing factor (EDRF). This epoch-making discovery answers the question raised for nearly one hundred years by pharmacologists about why vascular smooth muscle is relaxed by acetylcholine, which however elicits contraction of the other smooth muscles. Because of its instability, the true chemical nature of EDRF was not easily identified. Several years later, several research groups independently found that the biological activities and biochemical properties of EDRF were identical... 

Chin et al. (1992) have su ested that oxidized LDL and high-density lipoprotein (HDL) inactivate endothelial cell-derived NO. NO inactivation was due to the oxidized lipids within the lipoprotein particles and was thought to be explained by a chemical reaction between the lipoproteins and NO. Other investigators have shown that relaxation of vascular smooth muscle by acetylcholine or bradykinin (endothelium-dependent vasodilators) is inhibited by LDL (Andrews etal., 1987). The role of NO in the modification of LDL is discussed in full detail in Chapter 2. 

EC-SOD is a copper-zinc enzyme located on endothelial cell surfaces. It is believed that EC-SOD binds to the vasculature via specific glycosaminoglycans — probably heparan sulphate on the endothelium. The association of EC-SOD with endothelial cell surfaces may indicate a cell-specific protective role. Eig/ity per cent of SOD activity in control, noninflamed synovial fluid is due to EC-SOD and its concentration is decreased by 50% in RA fluid (Marklund etal., 1986). 

Injury (either physical or chemical) to the comeal endothelial cells has a marked efiect on occular function as these cells are responsible for maintaining the thickness and clarity of the cornea, yet they cannot be replaced if damaged. Immunohistochemical studies have revealed that enzymatic antioxidant defences, SOD, CAT and GSHPx, are similarly distributed in the corneal epithelium and endothelium (Rao etal., 1985 Attala et d., 1987, 1988). Other antioxidants include ascorbate, carotenoids and vitamin E (Fleath, 1962). 

The normal arterial wall consists of the intima, media, and adventitia, as illustrated in Fig. 4—3A. The endothelium is located in the intima and consists of a layer of endothelial cells that line the lumen of the artery and form a selective barrier between the vessel wall and blood contents. The internal elastic lamina separates the intima and media, where vascular smooth muscle cells are found. The vascular adventitia comprises the artery s outer layer. Atherosclerotic lesions form in the subendothelial space between the endothelial cells and internal elastic lamina. 

Fig. 4. The role of RANTES in recruiting monocytes and T lymphocytes to injured endothelium involves the binding of platelets to activated endothelium in a P-selectin-dependent manner with subsequent secretion of RANTES by bound platelets. RANTES can then attract CCR5-expressing monocytes and T cells to the damaged endothelium as well as causing monocyte firm adhesion to occur via binding to platelet-derived RANTES deposited on the endothelial cell layer.

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... 

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