Shear stress regulation

DeMaio L, Chang YS, Gardner TW, Tarbell JM, and Antonetti DA [2001] Shear stress regulates Occludin content and phosphorylation. Am J Physiol 28LH105-H113... 

Platt, M.O., et al. Cyclic pressure and shear stress regulate matrix metaUoproteinases and cathepsin activity in porcine aortic valves. J. Heart Valve Dis. 15(5), 622-629 (2006)... 

Atherosclerosis, a disease of the vascular wall, is the substrate for the arterial forms of CVD. Atherosclerotic plaques exhibit a focal distribution along the arterial tree as a consequence of local conditions that favor their initiation and progression. Low or reversed shear stress, for example, contributes to plaque development, a process in which the regulation of several genes may be involved (Resnick and Gimbrone 1995). 

Figure 11.30 Mechanisms of regulation of phospholipase A2. In all these processes described above, it is phospholipase A that carries out the hydrolysis of membrane phospholipid. Cytokines are local hormones produced by immune cells, T-lymphocytes and macrophages (Chapter 17). Other factors relate to shear stress in endothelial cells and those that stimulate release of granules from mast cells. Eicosanoids are present in the granules and they must be re-synthesised after degranulation in the mast cells. Here the enzymes described above must be present in mast cells.

Tsuruta, D., and Jones, J. G. (2003). The vimentin cytoskeleton regulates focal contact size and adhesion of endothelial cells subjected to shear stress. J. Cell Sci. 116, 4977-4984. 

Osteoblast intracellular calcium is regulated by membrane stretch or shear stress and by other mechanisms (Kamioka et al., 2006). Further, the absence of stretch causes atrophy. This effect is important, with acute and severe bone loss caused by disuse or unweighting (Bikle and Halloran, 1999). Stretch-induced calcium... 

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],... 

Kamiya, A., Bukhari, R., and Togawa, T. (1984) Adaptive regulation of wall shear stress optimizing vascular tree function. Bulletin of Mathematical Biology 46 127-137... 

Brakemeier, S., Kersten, A., Eichler, I., Grgic, I., Zakrzewicz, A., Hopp, H., Kohler, R., and Hoyer, J. 2003. Shear stress-induced up-regulation of the intermediate-conductance Ca2+-activated K+ channel in human endothelium. Cardiovasc. Res. 60 488 196. 

There are numerous reports in the literature regarding Ca -independent regulation of eNOS in response to stimuli such as estradiol and shear stress where an increase in NO production is not accomjpanied by an increase in intracellular Ca. Agonists that stimulate NO production in a Ca " -independent manner still however require a basal intracellular... 

PGI2. In vitro stndies have shown that COX-2 expression is up-regulated in endothelial cells by laminar shear stress (73). Furthermore, selective COX-2 inhibitors reduce systemic PGI-2 production in healthy volunteers (74). The clinical implications of these observations are unknown. In theory, COX-2 selective NSAIDs might increase the risk of thromboembolic cardiovascular events because of preferential inhibition of endothehal prostacychn synthesis without corresponding inhibition of platelet thromboxane synthesis, but no rehable data are available on the occurrence of cardiovascnlar events in patients treated with COX-2 selective or non-selective NSAIDs. 

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. 

The nitrates act by releasing nitric oxide, which relaxes vascular smooth muscle. The discovery that endothelium-derived relaxing factor (EDRF) is nitric oxide (1) stimulated new interest in these drugs, as nitric oxide not only controls local vessel wall tension in response to shear stress, but also plays a role in regulating the interaction of platelets with blood vessel walls. The release of nitric oxide from the walls of atheromatous arteries is reduced, because of malfunctioning or absent endothelium. Atheromatous arteries behave differently from healthy arteries, in that these vessels vasoconstrict rather than vasodilate when stimulated by acetylcholine. This impairment of the acetylcholine vasomotor response appears to be related to serum cholesterol concentration (2). 

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. 

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. ... 

Uematsu, M., Ohara, Y., Navas, J.P., Nishida, K., Murphy, T.J., Alexander, R.W., Nerem, R.M., and Harrison, D.G. (1995). Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am. J. Physiol. 269 C1371-C1378. 

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... 

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