Shear stress, endothelial cell response

Modulation of Endothelial Cell Response to Shear Stress... 

Bruder, J.L., Hsieh, T.C., Lerea, K.M., Olson, S.C., and Wu, J.M., Cell biological and biochemical analysis of induced cytoskeletal changes in bovine artery endothelial cells by resveratrol and the accompanying modified responses to arterial shear stress, BMC Cell Biol, 2, 1, 2001. 

Malek, A.M., Izumo, S. Mechanism of endothelial cell shape change and C5doskelet-al remodeling in response to fluid shear stress. J. Cell Sci. 109(Pt 4), 713-726 (1996)... 

Ando, J. and K. Yamamoto. 2009. Vascular mechanobiology Endothelial cell responses to fluid shear stress. Ore/73(11) 1983-92. 

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). 

Osteocytes also rapidly release nitric oxide in response to stress [160, 105] and this NO response seems to be required for the stress-related prostaglandin release [105]. Therefore, the behavior of osteocytes compares to that of endothelial cells which regulate the flow of blood through the vascular system, and also respond to fluid flow of 0.5 Pa with increased prostaglandin and nitric oxide production [79]. The response of endothelial cells to shear stress is likely related to their role in mediating an adaptive remodeling of the vasculature, so as to maintain constant endothelial fluid shear stress throughout the arterial site of the circulation [99],... 

Khachigian LM, Resnick N, Gimbrone MA Jr, Collins T. Nuclear factor-KB interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. / Clin Invest. 1995 96 1169-1175. 

Topper JN, Cai J, Falb D, Gimbrone MA Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci USA 1996 93(19) 10417-22. 

Hirata et al. [4] have noted that activated endothelial cells had increased endothelial lipase mRNA. Jaye et al. found that, upon stimulation with phorbol ester, the intensity of both 68 and 40 kDa bands increased in HCAEC and new bands of approximately 55 kDa, 38 and 36 kDa appeared in both HCAEC and HUVEC upon stimulation [3]. These new bands were not characterized, but may represent alternative splice products or an enzymatic cleavage product. Hirata et al. demonstrated that the expression of endothelial lipase is regulated by cytokines, by fluid shear stress and by cyclic stretch [18]. Using both HUVEC and HCAEC, they examined the effects of IL-1/ and TNF-a on endofhelial hpase mRNA levels. Exposure to IL-1/ for 24 h resulted in a 6.5-fold increase in EL mRNA in both HUVEC and HCAEC. TNF-a produced a ca. 4-fold increase in EL mRNA. The same group examined the response of both HUVEC and HCAEC to shear stress, and found a 2-3-fold increase in EL mRNA after 6 h of exposure. Additionally, cyclic stretch resulted in a 2.7-fold increase in EL mRNA. They concluded fhat EL expression is highly regulated by factors implicated in fhe development of vascular disease. 

Perhaps the most satisfying hypothesis for the formation of atherosclerotic lesions is that of response to injury in which lesions are precipitated by some form of injury to endothelial cells. The injury may be caused by elevated plasma levels of LDL and modified LDL (oxidized LDL), free radicals (e.g., caused by cigarette smoking), diabetes mellitus, hypertension-induced shear stress, and other factors that lead to focal desquamation of endothelial cells such as elevated plasma homocysteine levels, genetic... 

Its formation in vascular endothelial cells, in response to chemical stimuli and to physical stimuli such as shear stress, maintains a vasodilator tone that is essential for the regulation of blood flow and pressure. NO also inhibits platelet aggregation and adhesion, inhibits leukocyte adhesion and modulates smooth muscle cell proliferation. NO is also synthesized in neurons of the central nervous system (CNS), where it acts as a neuromediator with many physiological functions, including the formation of memory, coordination between neuronal activity and blood flow, and modulation of pain. In the peripheral nervous system, NO is now known to be the mediator released by a widespread network of nerves. ... 

Occludin phosphorylation may provide a molecular mechanism to control barrier properties. Studies from our group have demonstrated that both VEGF and shear stress induce permeability across endothelial monolayers associated with a rapid phosphorylation of occludin (67,68). The occludin phosphorylation was attenuated by a non-hydrolyzable cAMP analog that also inhibits shear-induced permeability (68). This phosphorylation of occludin appears to be serine or threonine directed since immunoprecipitation of occludin and phosphotyrosine blotting did not reveal any evidence of occludin tyrosine phosphorylation in this cell system (unpublished observation). However, in epithelial cells, evidence of occludin tyrosine phosphorylation exists (69). In addition, others have identified occludin phosphorylation in response to histamine (70) and use of brain extracts has helped identify casein kinase II as an occludin kinase (71). Collectively, this work demonstrates a close association of occludin phosphorylation with permeability. Future studies identifying specific occludin phosphorylation sites, followed by mutational analysis, should reveal the functional significance of occludin phosphorylation. 

P450 8A1 is constitutively expressed in human endothelial cells . The human CYP8A1 gene (chromosome 20) has 10 exons and has consensus sequences for Spl, AP-2, an interferon--/ response element, GATA NF, B, a CACCC box, glucocorticoid receptor, and a shear stress responsive element (GAGACC) . Whether or not all of these are functional and how they interact to maintain constitutive expression is not well understood yet. 

NOS III is found to be constitutively expressed in endothelial cells and some other cell types (see below). Some mechanisms that also regulate the expression of the NOS III gene have been described. Shear stress produced by the flowing blood not only increases endothelial NO release acutely (Lamontagne etal., 1992) but also up-regulates NOS III expression (Nishida et al., 1992). A putative shear stress-responsive element has been described... 

The involvement of Ca in the signal transduction pathway that translates shear stress into an immediate increase in NOS activity has, for some time, been controversial, and the response to shear stress has often been confused with mechanical perturbation. Recent data obtained using more sophisticated techniques have established that shear stress indeed increases [Ca ]j both in cultured cells and in endothelial cells in situ (Falcone et al.,... 

FIGURE 2 Inhibition of shear stress-induced release of nitric oxide in isolated endothelial cells by S-nitroso-N-acetylpenicillamine (SNAP). Relaxant responses of the first arterial strip in a three-tissue cascade are illustrated. The flow rate through the column of endothelial cells was varied from 0.3 to 3 ml/min. Three sets of control responses were obtained at 15-min intervals before the addition of SNAP. After the third set of control responses, 1 /rmol/liter SNAP was perfused through the column for 15 min (positioned away from the target arterial strips), following which the column was perfused with plain Krebs bicarbonate solution for a further 15 min. The perfusate was then directed over the target strips, and responses to shear stress were obtained. Data represent the means se from at least four separate experiments. 

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