Endothelial cells vascular, functions

Hill JM, Zalos G, HalcoxJR et al, Circulating endothelial progenitor cells, vascular function, and cardiovascular risk, N EnglJ Med 2003 348 593-600. 

Macklin, K.D., Mans, A.D.I, Pereira, E.P.R., Albuquerque, E.X., and Conti-Fine, B.M. 1998. Human vascular endothelial cells express functional nicotinic acetylcholine receptors. JPharmacol Expt Therapeut 287, 435-439. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

The endothelium has many diverse functions that enable it to participate in in-flammatoiy reactions (H27). These include modulation of vascular tone, and hence control of local blood flow changes in structure that allow leakage of fluids and plasma proteins into extravascular tissues local accumulation and subsequent extravasation into tissues of leukocytes and synthesis of surface molecules and soluble factors involved in leukocyte activation (B43). The endothelial cells themselves can modulate vascular tone by the release of vasoactive substances such as prostacyclin, nitric oxide (NO), ET. Endothelium-derived vasoactive substances... 

It has been proposed that NO mediates the myocardial depression associated with sepsis (F6, L14). NO synthesis induced by endotoxin blunts beta-adrenergic responsiveness (B2). In vivo, the use of NO synthase inhibitors led to conflicting results (M26), with a general decreased cardiac output and oxygen delivery being observed. NO synthase inhibition improved left ventricular contractility in endo-toxemic pigs but also increased ventricular afterloads, which ultimately is detrimental to cardiac function (H20). Possible sources of NO in the heart may be the vascular cells, the endothelial cells, and the cardiac myocytes (P6). 

E9. Endo, S., Inada, K., Yamada, Y., Takakuwa, T., Nakae, H., Kasai, T Koike, S., Inoue, Y., Nii-mi, M Wakabayashi, G and Taniguchi, S Functional modification of vascular endothelial cells by cytokines during septic shock. Res. Commun. Mol. Pathol. Pharmacol. 96, 23-38 (1996). 

Release of markers bound to the endothelial cell such as thrombomodulin is indicative of vascular damage. Increased levels of soluble thrombomodulin in plasma are diagnostic (93). Other endothelium-derived markers such as 6-keto-prostaglandin F a, which is a metabolite of prostacyclin, are useful in the assessment of endothelial function, with lower levels indicative of inability to synthesize this marker due to defective or damaged endothelium through plaque formation (93). 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

Screening the molecular heterogeneity of receptor expression in endothelial cell surfaces is required for the development of vascular-targeted therapies. First, as opposed to targeting purified proteins as discussed above, membrane-bound receptors are more likely to preserve their functional conformation, which can be lost upon purification and immobilization outside the context of intact cells. Moreover, many cell surface receptors require the cell membrane microenvironment to function so that protein-protein interaction may occur. Finally, combinatorial approaches may allow the selection of cell membrane ligands in a functional assay and without any bias about the cellular surface receptor. Therefore, even as yet unidentified receptors may be targeted. 

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