The Experts below are selected from a list of 65487 Experts worldwide ranked by ideXlab platform
Michael A Gimbrone - One of the best experts on this subject based on the ideXlab platform.
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Vascular Endothelium hemodynamics and the pathobiology of atherosclerosis
Cardiovascular Pathology, 2013Co-Authors: Michael A Gimbrone, Guillermo GarciacardenaAbstract:The localization of atherosclerotic lesion formation to regions of disturbed blood flow associated with certain arterial geometries, in humans and experimental animals, suggests an important role for hemodynamic forces in the pathobiology of atherosclerosis. There is increasing evidence that the Vascular Endothelium, which is directly exposed to various fluid mechanical forces generated by pulsatile blood flow, can discriminate among these different biomechanical stimuli and transduce them into genetic regulatory programs that modulate endothelial function. In this brief review, we discuss how biomechanical stimuli generated by blood flow can influence endothelial functional phenotypes, and explore the working hypothesis of "atheroprone" hemodynamic environments as "local risk factors" in atherogenesis. In addition, we consider the therapeutic implications of the activation of "atheroprotective genes" and their role as "critical regulatory nodes" in Vascular homeostasis.
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mcp 1 and il 8 trigger firm adhesion of monocytes to Vascular Endothelium under flow conditions
Nature, 1999Co-Authors: Robert E Gerszten, Eduardo A Garciazepeda, Han A Ding, Francis W Luscinskas, Michael A Gimbrone, Andrew D Luster, Masayuki Yoshida, Anthony RosenzweigAbstract:Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in Vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with Vascular Endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to Vascular Endothelium reveals an unexpected role for this chemokine in monocyte recruitment.
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mcp 1 and il 8 trigger firm adhesion of monocytes to Vascular Endothelium under flow conditions
Nature, 1999Co-Authors: Robert E Gerszten, Eduardo A Garciazepeda, Han A Ding, Francis W Luscinskas, Michael A Gimbrone, Andrew D Luster, Masayuki Yoshida, Anthony RosenzweigAbstract:Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in Vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with Vascular Endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to Vascular Endothelium reveals an unexpected role for this chemokine in monocyte recruitment.
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Vascular Endothelium responds to fluid shear stress gradients
Arteriosclerosis Thrombosis and Vascular Biology, 1992Co-Authors: Natacha Depaola, Peter F Davies, Michael A Gimbrone, C Forbes DeweyAbstract:In vitro investigations of the responses of Vascular Endothelium to fluid shear stress have typically been conducted under conditions where the time-mean shear stress is uniform. In contrast, the in vitro experiments reported here have re-created the large gradients in surface fluid shear stress found near arterial branches in vivo; specifically, we have produced a disturbed-flow region that includes both flow separation and reattachment. Near reattachment regions, shear stress is small but its gradient is large. Cells migrate away from this region, predominantly in the downstream direction. Those that remain divide at a rate that is high compared with that of cells subjected to uniform shear. We speculate that large shear stress gradients can induce morphological and functional changes in the Endothelium in regions of disturbed flow in vivo and thus may contribute to the formation of atherosclerotic lesions.
Eva Brand - One of the best experts on this subject based on the ideXlab platform.
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soluble adenylyl cyclase sac regulates calcium signaling in the Vascular Endothelium
The FASEB Journal, 2019Co-Authors: Mirja Mewes, Boris Schmitz, Stefanmartin Brand, Malte Lenders, Franciska Stappers, David Scharnetzki, Johanna Nedele, Johannes Fels, Roland Wedlichsoldner, Eva BrandAbstract:The Vascular Endothelium acts as a selective barrier between the bloodstream and extraVascular tissues. Intracellular [Ca2+]i signaling is essential for vasoactive agonist–induced stimulation of en...
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aldosterone signaling and soluble adenylyl cyclase a nexus for the kidney and Vascular Endothelium
Biochimica et Biophysica Acta, 2014Co-Authors: Boris Schmitz, Stefanmartin Brand, Eva BrandAbstract:The steroid hormone aldosterone regulates the reabsorption of water and ions in the kidney and plays a central role in blood pressure regulation and homeostasis. In recent years, the Vascular Endothelium has been established as an important aldosterone target organ with major implications in renal and cardioVascular health and disease. Different lines of evidence suggest that the calcium- and bicarbonate-activated soluble adenylyl cyclase (sAC) is a novel mediator of aldosterone signaling in both the kidney and Vascular Endothelium. This review summarizes our current understanding of the molecular mechanisms of sAC gene expression regulation in the kidney and Vascular Endothelium and outlines the potential clinical implications of sAC in chronic kidney disease and cardioVascular disease. This review is part of a special issue entitled: The role of soluble adenylyl cyclase in health and disease. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.
Francis W Luscinskas - One of the best experts on this subject based on the ideXlab platform.
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icam 1 regulates neutrophil adhesion and transcellular migration of tnf α activated Vascular Endothelium under flow
Blood, 2005Co-Authors: Lin Yang, Tracey E Sciuto, Ann M. Dvorak, Richard M Froio, Ronen Alon, Francis W LuscinskasAbstract:In vivo, leukocyte transendothelial migration (TEM) occurs at endothelial cell junctions (paracellular) and nonjunctional (transcellular) locations, whereas in vitro models report that TEM is mostly paracellular. The mechanisms that control the route of leukocyte TEM remain unknown. Here we tested the hypothesis that elevated intercellular adhesion molecule-1 (ICAM-1) expression regulates the location of polymorphonuclear leukocyte (PMN) TEM. We used an in vitro flow model of tumor necrosis factor-α (TNF-α)-activated human umbilical vein Endothelium cells (HUVECs) or an HUVEC cell line transfected with ICAM-1GFP (green fluorescent protein) and live-cell fluorescence microscopy to quantify the location of PMN adhesion and TEM. We observed robust transcellular TEM with TNF-α-activated HUVECs and ICAM-1GFP immortalized HUVECS (iHUVECs). In contrast, primary CD3+ T lymphocytes exclusively used a paracellular route. Endothelial ICAM-1 was identified as essential for both paracellular and transcellular PMN transmigration, and interfering with ICAM-1 cytoplasmic tail function preferentially reduced transcellular TEM. We also found that ICAM-1 surface density and distribution as well as endothelial cell shape contributed to transcellular TEM. In summary, ICAM-1 promotes junctional and nonjunctional TEM across inflamed Vascular Endothelium via distinct cytoplasmic tail associations. (Blood. 2005;106:584-592)
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mcp 1 and il 8 trigger firm adhesion of monocytes to Vascular Endothelium under flow conditions
Nature, 1999Co-Authors: Robert E Gerszten, Eduardo A Garciazepeda, Han A Ding, Francis W Luscinskas, Michael A Gimbrone, Andrew D Luster, Masayuki Yoshida, Anthony RosenzweigAbstract:Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in Vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with Vascular Endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to Vascular Endothelium reveals an unexpected role for this chemokine in monocyte recruitment.
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mcp 1 and il 8 trigger firm adhesion of monocytes to Vascular Endothelium under flow conditions
Nature, 1999Co-Authors: Robert E Gerszten, Eduardo A Garciazepeda, Han A Ding, Francis W Luscinskas, Michael A Gimbrone, Andrew D Luster, Masayuki Yoshida, Anthony RosenzweigAbstract:Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in Vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with Vascular Endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to Vascular Endothelium reveals an unexpected role for this chemokine in monocyte recruitment.
Anthony Rosenzweig - One of the best experts on this subject based on the ideXlab platform.
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mcp 1 and il 8 trigger firm adhesion of monocytes to Vascular Endothelium under flow conditions
Nature, 1999Co-Authors: Robert E Gerszten, Eduardo A Garciazepeda, Han A Ding, Francis W Luscinskas, Michael A Gimbrone, Andrew D Luster, Masayuki Yoshida, Anthony RosenzweigAbstract:Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in Vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with Vascular Endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to Vascular Endothelium reveals an unexpected role for this chemokine in monocyte recruitment.
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mcp 1 and il 8 trigger firm adhesion of monocytes to Vascular Endothelium under flow conditions
Nature, 1999Co-Authors: Robert E Gerszten, Eduardo A Garciazepeda, Han A Ding, Francis W Luscinskas, Michael A Gimbrone, Andrew D Luster, Masayuki Yoshida, Anthony RosenzweigAbstract:Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in Vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with Vascular Endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to Vascular Endothelium reveals an unexpected role for this chemokine in monocyte recruitment.
Lowell B Langille - One of the best experts on this subject based on the ideXlab platform.
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shear stress regulates forward and reverse planar cell polarity of Vascular Endothelium in vivo and in vitro
Circulation Research, 2006Co-Authors: Shannon Mccue, Dorota Dajnowiec, Ming Zhang, Moira R Jackson, Lowell B LangilleAbstract:Cultured Vascular Endothelium displays profound morphological adaptations to shear stress that include planar cell polarity (PCP) that is directed downstream. Endothelial cells in blood vessels are also polarized; however, the direction of polarity is vessel specific, and shear-independent mechanisms have been inferred. The regulation of endothelial PCP is therefore controversial. We report that the direction of PCP in blood vessels is age and vessel specific; nonetheless, it is caused by shear-related regulation of glycogen synthase kinase-3β (GSK-3β), a profound regulator of endothelial microtubule stability. When GSK-3β is inhibited, PCP reverses direction. Endothelium is the only cell type studied to date that can reverse direction of polarity. Tight regulation of GSK-3β, microtubule dynamics, and cell polarity was also required for the striking morphological responses of Endothelium to shear stress (cell elongation and orientation with shear). Finally, the cytoskeletal polarity displayed in blood vessels is associated with polarized (shear-directed) cell mitoses that have important effects on endothelial repair. Vascular Endothelium therefore displays a novel mode of mechanosensitive PCP that represents the first example of a single cell type that can reverse direction of polarity.
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shear stress regulates forward and reverse planar cell polarity of Vascular Endothelium in vivo and in vitro
Circulation Research, 2006Co-Authors: Shannon Mccue, Dorota Dajnowiec, Ming Zhang, Moira R Jackson, Lowell B LangilleAbstract:Cultured Vascular Endothelium displays profound morphological adaptations to shear stress that include planar cell polarity (PCP) that is directed downstream. Endothelial cells in blood vessels are also polarized; however, the direction of polarity is vessel specific, and shear-independent mechanisms have been inferred. The regulation of endothelial PCP is therefore controversial. We report that the direction of PCP in blood vessels is age and vessel specific; nonetheless, it is caused by shear-related regulation of glycogen synthase kinase-3beta (GSK-3beta), a profound regulator of endothelial microtubule stability. When GSK-3beta is inhibited, PCP reverses direction. Endothelium is the only cell type studied to date that can reverse direction of polarity. Tight regulation of GSK-3beta, microtubule dynamics, and cell polarity was also required for the striking morphological responses of Endothelium to shear stress (cell elongation and orientation with shear). Finally, the cytoskeletal polarity displayed in blood vessels is associated with polarized (shear-directed) cell mitoses that have important effects on endothelial repair. Vascular Endothelium therefore displays a novel mode of mechanosensitive PCP that represents the first example of a single cell type that can reverse direction of polarity.
