The Experts below are selected from a list of 77562 Experts worldwide ranked by ideXlab platform
Stefan Offermanns - One of the best experts on this subject based on the ideXlab platform.
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lpa1 receptor mediated thromboxane a2 release is responsible for lysophosphatidic acid induced Vascular Smooth Muscle contraction
The FASEB Journal, 2017Co-Authors: Peter T Dancs, Stefan Offermanns, Eva Ruisanchez, Andrea Balogh, Cecilia Rita Panta, Zsuzsanna Miklos, Rolf M Nusing, Junken Aoki, Jerold Chun, Gabor TigyiAbstract:Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate Vascular Smooth Muscle cells (VSM...
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previously differentiated medial Vascular Smooth Muscle cells contribute to neointima formation following Vascular injury
Vascular Cell, 2014Co-Authors: Brian Paul Herring, April M Hoggatt, Christopher Burlak, Stefan OffermannsAbstract:Background The origins of neointimal Smooth Muscle cells that arise following Vascular injury remains controversial. Studies have suggested that these cells may arise from previously differentiated medial Vascular Smooth Muscle cells, resident stem cells or blood born progenitors. In the current study we examined the contribution of the previously differentiated Vascular Smooth Muscle cells to the neointima that forms following carotid artery ligation.
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previously differentiated medial Vascular Smooth Muscle cells contribute to neointima formation following Vascular injury
PMC, 2014Co-Authors: Brian Paul Herring, April M Hoggatt, Christopher Burlak, Stefan OffermannsAbstract:The origins of neointimal Smooth Muscle cells that arise following Vascular injury remains controversial. Studies have suggested that these cells may arise from previously differentiated medial Vascular Smooth Muscle cells, resident stem cells or blood born progenitors. In the current study we examined the contribution of the previously differentiated Vascular Smooth Muscle cells to the neointima that forms following carotid artery ligation. We utilized transgenic mice harboring a cre recombinase-dependent reporter gene (mTmG). These mice express membrane targeted tandem dimer Tomato (mTomato) prior to cre-mediated excision and membrane targeted EGFP (mEGFP) following excision. The mTmG mice were crossed with transgenic mice expressing either Smooth Muscle myosin heavy chain (Myh11) or Smooth Muscle α-actin (Acta2) driven tamoxifen regulated cre recombinase. Following treatment of adult mice with tamoxifen these mice express mEGFP exclusively in differentiated Smooth Muscle cells. Subsequently Vascular injury was induced in the mice by carotid artery ligation and the contribution of mEGFP positive cells to the neointima determined. Analysis of the cellular composition of the neointima that forms following injury revealed that mEGFP positive cells derived from either Mhy11 or Acta2 tagged medial Vascular Smooth Muscle cells contribute to the majority of neointima formation (79 ± 17% and 81 ± 12%, respectively). These data demonstrate that the majority of the neointima that forms following carotid ligation is derived from previously differentiated medial Vascular Smooth Muscle cells.
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micrornas are necessary for Vascular Smooth Muscle growth differentiation and function
Arteriosclerosis Thrombosis and Vascular Biology, 2010Co-Authors: Sebastian Albinsson, Stefan Offermanns, Yajaira Suarez, Athanasia Skoura, Joseph M Miano, William C SessaAbstract:Objective— Regulation of Vascular Smooth Muscle (VSM) proliferation and contractile differentiation is an important factor in Vascular development and subsequent cardioVascular diseases. Recently, ...
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role for g12 g13 in agonist induced Vascular Smooth Muscle cell contraction
Circulation Research, 2000Co-Authors: Antje Gohla, Gunter Schultz, Stefan OffermannsAbstract:Abstract —Receptor-induced Vascular Smooth Muscle cell contraction is mediated by dual regulation of myosin light chain (MLC20) phosphorylation through Ca2+-dependent stimulation of myosin light chain kinase and Rho/Rho-kinase–mediated inhibition of myosin phosphatase. Although myosin light chain kinase regulation is initiated by the coupling of receptors to G proteins of the Gq family, Gq and G11, it is not known how receptors regulate the Rho/Rho-kinase–mediated pathway. In Vascular Smooth Muscle cells, receptor-mediated MLC20 phosphorylation and cell contraction was blocked by inhibitors of each of the pathways. Receptors of various vasocontractors were found to couple to Gq/G11 and G12/G13, and constitutively active forms of Gα12 and Gα13 induced a pronounced contraction of Vascular Smooth Muscle cells that could be blocked by C3 exoenzyme, by inhibition of Rho-kinase, and by stable analogues of cGMP and cAMP. Receptor-mediated Smooth Muscle cell contraction was strongly inhibited by dominant-negative forms of Gα12 and Gα13. These data indicate that a G12/G13-mediated Rho/Rho-kinase–dependent pathway operates in Smooth Muscle cells and that dual regulation of MLC20 phosphorylation by vasocontractors is initiated by the dual coupling of their receptors to G proteins of the Gq and G12 families.
Kathy K Griendling - One of the best experts on this subject based on the ideXlab platform.
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upregulation of nox1 in Vascular Smooth Muscle leads to impaired endothelium dependent relaxation via enos uncoupling
American Journal of Physiology-heart and Circulatory Physiology, 2010Co-Authors: Anna Dikalova, David G Harrison, Maria Carolina Gongora, David J Lambeth, Sergey Dikalov, Kathy K GriendlingAbstract:Recent work has made it clear that oxidant systems interact. To investigate potential cross talk between NADPH oxidase (Nox) 1 upregulation in Vascular Smooth Muscle and endothelial function, trans...
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nox4 is required for maintenance of the differentiated Vascular Smooth Muscle cell phenotype
Arteriosclerosis Thrombosis and Vascular Biology, 2007Co-Authors: Roza E Clempus, Dan Sorescu, Anna Dikalova, Lily Pounkova, George P Sorescu, Bernard Lassegue, Kathy K GriendlingAbstract:Objective— The mechanisms responsible for maintaining the differentiated phenotype of adult Vascular Smooth Muscle cells (VSMCs) are incompletely understood. Reactive oxygen species (ROS) have been...
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reactive oxygen species signaling in Vascular Smooth Muscle cells
Cardiovascular Research, 2006Co-Authors: Roza E Clempus, Kathy K GriendlingAbstract:Reactive oxygen species (ROS) have been shown to function as important signaling molecules in the cardioVascular system. Vascular Smooth Muscle cells (VSMCs) contain several sources of ROS, among which the NADPH oxidases are predominant. In VSMCs, ROS mediate many pathophysiological processes, such as growth, migration, apoptosis and secretion of inflammatory cytokines, as well as physiological processes, such as differentiation, by direct and indirect effects at multiple signaling levels. Therefore, it becomes critical to understand the different roles ROS play in the physiology and pathophysiology of VSMCs.
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angiotensin ii induced hypertrophy is potentiated in mice overexpressing p22phox in Vascular Smooth Muscle
American Journal of Physiology-heart and Circulatory Physiology, 2005Co-Authors: David S Weber, Petra Rocic, Adamantios M Mellis, Karine Laude, Alicia N Lyle, David G Harrison, Kathy K GriendlingAbstract:Increased reactive oxygen species (ROS) are implicated in several Vascular pathologies associated with Vascular Smooth Muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (...
Nancy L Sehgel - One of the best experts on this subject based on the ideXlab platform.
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augmented Vascular Smooth Muscle cell stiffness and adhesion when hypertension is superimposed on aging
Hypertension, 2015Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Michael A Hill, Dorothy E Vatner, Stephen F Vatner, Gerald A MeiningerAbstract:Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the Vascular wall. Alternatively, we hypothesized that a significant component of increased Vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of Vascular Smooth Muscle cells, and that aging would augment the contribution from Vascular Smooth Muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar–Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar–Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar–Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both Vascular Smooth Muscle cell stiffness and Vascular Smooth Muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of Vascular Smooth Muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
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augmented Vascular Smooth Muscle cell stiffness and adhesion when hypertension is superimposed on aging
Hypertension, 2015Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Michael A Hill, Dorothy E Vatner, Stephen F Vatner, Zhe Sun, Gerald A MeiningerAbstract:Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the Vascular wall. Alternatively, we hypothesized that a significant component of increased Vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of Vascular Smooth Muscle cells, and that aging would augment the contribution from Vascular Smooth Muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both Vascular Smooth Muscle cell stiffness and Vascular Smooth Muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of Vascular Smooth Muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
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Increased Vascular Smooth Muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension
American journal of physiology. Heart and circulatory physiology, 2013Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Dorothy E Vatner, Gerald A Meininger, J. Trzeciakowski, Yi Zhu, Zhe Sun, Stephen F VatnerAbstract:Increased Vascular stiffness is fundamental to hypertension, and its complications, including atherosclerosis, suggest that therapy should also be directed at Vascular stiffness, rather than just the regulation of peripheral Vascular resistance. It is currently held that the underlying mechanisms of Vascular stiffness in hypertension only involve the extracellular matrix and endothelium. We hypothesized that increased large-artery stiffness in hypertension is partly due to intrinsic mechanical properties of Vascular Smooth Muscle cells. After confirming increased arterial pressure and aortic stiffness in spontaneously hypertensive rats, we found increased elastic stiffness of aortic Smooth Muscle cells of spontaneously hypertensive rats compared with Wistar-Kyoto normotensive controls using both an engineered aortic tissue model and atomic force microscopy nanoindentation. Additionally, we observed different temporal oscillations in the stiffness of Vascular Smooth Muscle cells derived from hypertensive and control rats, suggesting that a dynamic component to cellular elastic stiffness is altered in hypertension. Treatment with inhibitors of Vascular Smooth Muscle cell cytoskeletal proteins reduced Vascular Smooth Muscle cell stiffness from hypertensive and control rats, suggesting their participation in the mechanism. This is the first study demonstrating that stiffness of individual Vascular Smooth Muscle cells mediates Vascular stiffness in hypertension, a novel concept, which may elucidate new therapies for hypertension and for Vascular stiffness.
Gerald A Meininger - One of the best experts on this subject based on the ideXlab platform.
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augmented Vascular Smooth Muscle cell stiffness and adhesion when hypertension is superimposed on aging
Hypertension, 2015Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Michael A Hill, Dorothy E Vatner, Stephen F Vatner, Gerald A MeiningerAbstract:Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the Vascular wall. Alternatively, we hypothesized that a significant component of increased Vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of Vascular Smooth Muscle cells, and that aging would augment the contribution from Vascular Smooth Muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar–Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar–Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar–Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both Vascular Smooth Muscle cell stiffness and Vascular Smooth Muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of Vascular Smooth Muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
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augmented Vascular Smooth Muscle cell stiffness and adhesion when hypertension is superimposed on aging
Hypertension, 2015Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Michael A Hill, Dorothy E Vatner, Stephen F Vatner, Zhe Sun, Gerald A MeiningerAbstract:Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the Vascular wall. Alternatively, we hypothesized that a significant component of increased Vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of Vascular Smooth Muscle cells, and that aging would augment the contribution from Vascular Smooth Muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both Vascular Smooth Muscle cell stiffness and Vascular Smooth Muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of Vascular Smooth Muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
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Increased Vascular Smooth Muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension
American journal of physiology. Heart and circulatory physiology, 2013Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Dorothy E Vatner, Gerald A Meininger, J. Trzeciakowski, Yi Zhu, Zhe Sun, Stephen F VatnerAbstract:Increased Vascular stiffness is fundamental to hypertension, and its complications, including atherosclerosis, suggest that therapy should also be directed at Vascular stiffness, rather than just the regulation of peripheral Vascular resistance. It is currently held that the underlying mechanisms of Vascular stiffness in hypertension only involve the extracellular matrix and endothelium. We hypothesized that increased large-artery stiffness in hypertension is partly due to intrinsic mechanical properties of Vascular Smooth Muscle cells. After confirming increased arterial pressure and aortic stiffness in spontaneously hypertensive rats, we found increased elastic stiffness of aortic Smooth Muscle cells of spontaneously hypertensive rats compared with Wistar-Kyoto normotensive controls using both an engineered aortic tissue model and atomic force microscopy nanoindentation. Additionally, we observed different temporal oscillations in the stiffness of Vascular Smooth Muscle cells derived from hypertensive and control rats, suggesting that a dynamic component to cellular elastic stiffness is altered in hypertension. Treatment with inhibitors of Vascular Smooth Muscle cell cytoskeletal proteins reduced Vascular Smooth Muscle cell stiffness from hypertensive and control rats, suggesting their participation in the mechanism. This is the first study demonstrating that stiffness of individual Vascular Smooth Muscle cells mediates Vascular stiffness in hypertension, a novel concept, which may elucidate new therapies for hypertension and for Vascular stiffness.
Stephen F Vatner - One of the best experts on this subject based on the ideXlab platform.
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augmented Vascular Smooth Muscle cell stiffness and adhesion when hypertension is superimposed on aging
Hypertension, 2015Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Michael A Hill, Dorothy E Vatner, Stephen F Vatner, Gerald A MeiningerAbstract:Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the Vascular wall. Alternatively, we hypothesized that a significant component of increased Vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of Vascular Smooth Muscle cells, and that aging would augment the contribution from Vascular Smooth Muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar–Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar–Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar–Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both Vascular Smooth Muscle cell stiffness and Vascular Smooth Muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of Vascular Smooth Muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
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augmented Vascular Smooth Muscle cell stiffness and adhesion when hypertension is superimposed on aging
Hypertension, 2015Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Michael A Hill, Dorothy E Vatner, Stephen F Vatner, Zhe Sun, Gerald A MeiningerAbstract:Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the Vascular wall. Alternatively, we hypothesized that a significant component of increased Vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of Vascular Smooth Muscle cells, and that aging would augment the contribution from Vascular Smooth Muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both Vascular Smooth Muscle cell stiffness and Vascular Smooth Muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of Vascular Smooth Muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
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Increased Vascular Smooth Muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension
American journal of physiology. Heart and circulatory physiology, 2013Co-Authors: Nancy L Sehgel, Zhongkui Hong, William C Hunter, Dorothy E Vatner, Gerald A Meininger, J. Trzeciakowski, Yi Zhu, Zhe Sun, Stephen F VatnerAbstract:Increased Vascular stiffness is fundamental to hypertension, and its complications, including atherosclerosis, suggest that therapy should also be directed at Vascular stiffness, rather than just the regulation of peripheral Vascular resistance. It is currently held that the underlying mechanisms of Vascular stiffness in hypertension only involve the extracellular matrix and endothelium. We hypothesized that increased large-artery stiffness in hypertension is partly due to intrinsic mechanical properties of Vascular Smooth Muscle cells. After confirming increased arterial pressure and aortic stiffness in spontaneously hypertensive rats, we found increased elastic stiffness of aortic Smooth Muscle cells of spontaneously hypertensive rats compared with Wistar-Kyoto normotensive controls using both an engineered aortic tissue model and atomic force microscopy nanoindentation. Additionally, we observed different temporal oscillations in the stiffness of Vascular Smooth Muscle cells derived from hypertensive and control rats, suggesting that a dynamic component to cellular elastic stiffness is altered in hypertension. Treatment with inhibitors of Vascular Smooth Muscle cell cytoskeletal proteins reduced Vascular Smooth Muscle cell stiffness from hypertensive and control rats, suggesting their participation in the mechanism. This is the first study demonstrating that stiffness of individual Vascular Smooth Muscle cells mediates Vascular stiffness in hypertension, a novel concept, which may elucidate new therapies for hypertension and for Vascular stiffness.
