The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform
Jesús Egido - One of the best experts on this subject based on the ideXlab platform.
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peptide inhibitor of nf κb translocation ameliorates Experimental Atherosclerosis
American Journal of Pathology, 2013Co-Authors: Benat Mallavia, Carlota Recio, Ainhoa Oguiza, Guadalupe Ortizmunoz, Iolanda Lazaro, Virginia Lopezparra, Oscar Lopezfranco, Susann G Schindler, Reinhard Depping, Jesús EgidoAbstract:Atherosclerosis is a chronic inflammatory disease of the arterial wall. NF-κB is a major regulator of inflammation that controls the expression of many genes involved in atherogenesis. Activated NF-κB was detected in human atherosclerotic plaques, and modulation of NF-κB inflammatory activity limits disease progression in mice. Herein, we investigate the anti-inflammatory and atheroprotective effects of a cell-permeable peptide containing the NF-κB nuclear localization sequence (NLS). In vascular smooth muscle cells and macrophages, NLS peptide specifically blocked the importin α-mediated nuclear import of NF-κB and prevented lipopolysaccharide-induced pro-inflammatory gene expression, cell migration, and oxidative stress. In Experimental Atherosclerosis (apolipoprotein E-knockout mice fed a high-fat diet), i.p., 0.13 μmol/day NLS peptide administration for 5 weeks attenuated NF-κB activation in atherosclerotic plaques. NLS peptide significantly inhibited lesion development at both early (age 10 weeks) and advanced (age 28 weeks) stages of Atherosclerosis in mice, without affecting serum lipid levels. Plaques from NLS-treated mice contained fewer macrophages of pro-inflammatory M1 subtype than those from respective untreated controls. By contrast, the relative smooth muscle cell and collagen content was increased, indicating a more stable plaque phenotype. NLS peptide also attenuated pro-inflammatory gene expression and oxidative stress in aortic lesions. Our study demonstrates that targeting NF-κB nuclear translocation hampers inflammation and Atherosclerosis development and identifies cell-permeable NLS peptide as a potential anti-atherosclerotic agent.
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HSP90 inhibition by 17-DMAG attenuates oxidative stress in Experimental Atherosclerosis.
Cardiovascular research, 2012Co-Authors: Julio Madrigal-matute, Carlos Ernesto Fernandez-garcia, Carmen Gomez-guerrero, Oscar Lopez-franco, Begoña Muñoz-garcía, Jesús Egido, Luis Miguel Blanco-colio, Jose Luis Martin-venturaAbstract:Aims Reactive oxygen species (ROS) participate in atherogenesis through different mechanisms including oxidative stress and inflammation. Proteins implicated in both processes, such as mitogen-activated protein kinase kinase (MEK) and some NADPH oxidase (NOX) subunits, are heat shock protein-90 (HSP90) client proteins. In this work, we investigated the antioxidant properties of the HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in Experimental Atherosclerosis. Methods and results Treatment of ApoE−/− mice with 17-DMAG (2 mg/kg every 2 days for 10 weeks) decreased ROS levels and extracellular signal-regulated kinase (ERK) activation in aortic plaques compared with control animals. Accordingly, treatment of rat vascular smooth muscle cells (VSMCs) with 17-DMAG increased HSP27 and HSP70 and inhibited ERK activation. Interestingly, 17-DMAG diminished NADPH oxidase dependent ROS production in VSMCs and monocytes. In addition, a marked reduction in NADPH oxidase dependent ROS production was observed with HSP90siRNA and the opposite pattern with HSP70siRNA. 17-DMAG also diminished the expression of Nox1 and Nox organizer-1 (Noxo1) in VSMCs and monocytes. Interestingly, 17-DMAG was able to modulate ROS-induced monocyte to macrophage differentiation. Finally, higher expression of Nox1 and Noxo1 was found in the inflammatory region of human atherosclerotic plaques, colocalizing with VSMCs, macrophages, and ROS-producing cells. Conclusion Our results suggest that HSP90 inhibitors interfere with oxidative stress and modulate Experimental Atherosclerosis development through reduction in pro-oxidative factors.
Roland Stocker - One of the best experts on this subject based on the ideXlab platform.
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protective effect of vitamin e supplements on Experimental Atherosclerosis is modest and depends on preexisting vitamin e deficiency
Free Radical Biology and Medicine, 2006Co-Authors: Cacang Suarna, Katherine Choy, Trevor A Mori, Kevin D Croft, Osamu Cynshi, Roland StockerAbstract:Abstract Vitamin E has failed to protect humans from cardiovascular disease outcome, yet its role in Experimental Atherosclerosis remains less clear. A previous study (Proc. Natl. Acad. Sci. USA 97:13830–13834; 2000) showed that vitamin E deficiency caused by disruption of the α-tocopherol transfer protein gene (Ttpa) is associated with a modest increase in Atherosclerosis in apolipoprotein E gene deficient (Apoe−/−) mice. Here we confirm this finding and report that in Apoe−/−Ttpa−/− mice dietary α-tocopherol (αT) supplements restored circulating and aortic levels of αT, and decreased Atherosclerosis in the aortic root to a level comparable to that seen in Apoe−/− mice. However, such dietary supplements did not decrease disease in Apoe−/− mice, whereas dietary supplements with a synthetic vitamin E analog (BO-653), either alone or in combination with αT, decreased Atherosclerosis in Apoe−/− and in Apoe−/−Ttpa−/− mice. Differences in Atherosclerosis were not associated with changes in the arterial concentrations of F2-isoprostanes and cholesterylester hydro(pero)xides, nor were they reflected in the resistance of plasma lipids to ex vivo oxidation. These results show that vitamin E at best has a modest effect on Experimental Atherosclerosis in hyperlipidemic mice, and only in situations of severe vitamin E deficiency and independent of lipid oxidation in the vessel wall.
Christopher K. Zarins - One of the best experts on this subject based on the ideXlab platform.
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reduction of aortic wall motion inhibits hypertension mediated Experimental Atherosclerosis
Arteriosclerosis Thrombosis and Vascular Biology, 2000Co-Authors: Bradford I. Tropea, Phil Huie, Richard K. Sibley, Severin P Schwarzacher, Albert Y Chang, Chris Asvar, Christopher K. ZarinsAbstract:Abstract —Hypertension is a well-known risk factor for coronary artery disease and carotid and lower extremity occlusive disease. Surgically induced hypertension in hypercholesterolemic animals results in increased aortic wall motion and increased plaque formation. We tested the hypothesis that reduction in aortic wall motion, despite continued hypertension, could reduce plaque formation. New Zealand White rabbits (n=26) underwent thoracic aortic banding to induce hypertension and were fed an atherogenic diet for 3 weeks. In 13 rabbits, a segment of aorta proximal to an aortic band was externally wrapped to reduce wall motion. All animals were fed an atherogenic diet for 3 weeks. Four groups were studied: 1, coarctation control (no wrap, n=7); 2, coarctation with loose wrap (n=6); 3, coarctation with firm wrap (n=7); and 4, control (noncoarcted, n=6). Wall motion, blood pressure, and pulse pressure were measured at standard reference sites proximal and distal to the coarctation by use of intravascular ultrasound. Quantitative morphometry was used to measure intimal plaque. Mean arterial pressure and cyclic aortic wall motion were equally increased proximal to the aortic coarctation in all 3 coarcted rabbit groups compared with the control group ( P <0.001). Wall motion in the segment of aorta under the loose and firm wraps was no different from the control value. The external wrap significantly reduced intimal thickening in the 4 groups by the following amounts: group 1, 0.30±0.03 mm2; group 2, 0.06±0.02 mm2; group 3, 0.04±0.02 mm2; and group 4, 0.01±0.01 mm2 ( P <0.001). Localized inhibition of aortic wall motion in the lesion-prone hypertensive aorta resulted in significant reduction in intimal plaque formation. These data suggest that arterial wall cyclic motion may stimulate cellular proliferation and lipid uptake in Experimental Atherosclerosis.
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Hypertension-enhanced monocyte adhesion in Experimental Atherosclerosis
Journal of vascular surgery, 1996Co-Authors: Bradford I. Tropea, Phil Huie, John P. Cooke, Philip S. Tsao, Richard K. Sibley, Christopher K. ZarinsAbstract:Purpose: Hypertension is a known clinical risk factor for Atherosclerosis. In Experimental Atherosclerosis, monocyte adhesion to the endothelial surface is enhanced and is considered to be an important early stage in plaque formation. We tested the hypothesis that hypertension enhances monocyte adhesion in Experimental Atherosclerosis. Methods: Twenty-two New Zealand White rabbits were fed an atherogenic diet for 3 weeks to induce plaque formation. Aortic coarctation was created in eight rabbits by wrapping a Dacron band around the midportion of the descending thoracic aorta (stenosis group), whereas six rabbits underwent banding without aortic constriction (no stenosis group). Eight rabbits served as nonoperated controls. Monocyte binding to the aortic endothelial surface was counted with epifluorescent microscopy on standard aortic segments proximal and distal to the band. Immunohistochemistry was performed for the following antibodies: VCAM-1, RAM11, CD11b, and factor VIII. Results: Mean blood ressure was 89±3 mm Hg in the aorta proximal to the stenosis, compared with 64±4 mm Hg in the no stenosis group and 74±3 mm Hg in the control group ( p p p p p Conclusions: In the hypertensive region in the aorta proximal to the stenosis, monocyte adhesion and endothelial VCAM-1 expression were increased, with intimal thickening and accumulation of macrophages. These findings suggest that hypertension may promote atherosclerotic plaque formation by enhancing monocyte adhesion.
Jose Luis Martin-ventura - One of the best experts on this subject based on the ideXlab platform.
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HSP90 inhibition by 17-DMAG attenuates oxidative stress in Experimental Atherosclerosis.
Cardiovascular research, 2012Co-Authors: Julio Madrigal-matute, Carlos Ernesto Fernandez-garcia, Carmen Gomez-guerrero, Oscar Lopez-franco, Begoña Muñoz-garcía, Jesús Egido, Luis Miguel Blanco-colio, Jose Luis Martin-venturaAbstract:Aims Reactive oxygen species (ROS) participate in atherogenesis through different mechanisms including oxidative stress and inflammation. Proteins implicated in both processes, such as mitogen-activated protein kinase kinase (MEK) and some NADPH oxidase (NOX) subunits, are heat shock protein-90 (HSP90) client proteins. In this work, we investigated the antioxidant properties of the HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in Experimental Atherosclerosis. Methods and results Treatment of ApoE−/− mice with 17-DMAG (2 mg/kg every 2 days for 10 weeks) decreased ROS levels and extracellular signal-regulated kinase (ERK) activation in aortic plaques compared with control animals. Accordingly, treatment of rat vascular smooth muscle cells (VSMCs) with 17-DMAG increased HSP27 and HSP70 and inhibited ERK activation. Interestingly, 17-DMAG diminished NADPH oxidase dependent ROS production in VSMCs and monocytes. In addition, a marked reduction in NADPH oxidase dependent ROS production was observed with HSP90siRNA and the opposite pattern with HSP70siRNA. 17-DMAG also diminished the expression of Nox1 and Nox organizer-1 (Noxo1) in VSMCs and monocytes. Interestingly, 17-DMAG was able to modulate ROS-induced monocyte to macrophage differentiation. Finally, higher expression of Nox1 and Noxo1 was found in the inflammatory region of human atherosclerotic plaques, colocalizing with VSMCs, macrophages, and ROS-producing cells. Conclusion Our results suggest that HSP90 inhibitors interfere with oxidative stress and modulate Experimental Atherosclerosis development through reduction in pro-oxidative factors.
Cacang Suarna - One of the best experts on this subject based on the ideXlab platform.
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protective effect of vitamin e supplements on Experimental Atherosclerosis is modest and depends on preexisting vitamin e deficiency
Free Radical Biology and Medicine, 2006Co-Authors: Cacang Suarna, Katherine Choy, Trevor A Mori, Kevin D Croft, Osamu Cynshi, Roland StockerAbstract:Abstract Vitamin E has failed to protect humans from cardiovascular disease outcome, yet its role in Experimental Atherosclerosis remains less clear. A previous study (Proc. Natl. Acad. Sci. USA 97:13830–13834; 2000) showed that vitamin E deficiency caused by disruption of the α-tocopherol transfer protein gene (Ttpa) is associated with a modest increase in Atherosclerosis in apolipoprotein E gene deficient (Apoe−/−) mice. Here we confirm this finding and report that in Apoe−/−Ttpa−/− mice dietary α-tocopherol (αT) supplements restored circulating and aortic levels of αT, and decreased Atherosclerosis in the aortic root to a level comparable to that seen in Apoe−/− mice. However, such dietary supplements did not decrease disease in Apoe−/− mice, whereas dietary supplements with a synthetic vitamin E analog (BO-653), either alone or in combination with αT, decreased Atherosclerosis in Apoe−/− and in Apoe−/−Ttpa−/− mice. Differences in Atherosclerosis were not associated with changes in the arterial concentrations of F2-isoprostanes and cholesterylester hydro(pero)xides, nor were they reflected in the resistance of plasma lipids to ex vivo oxidation. These results show that vitamin E at best has a modest effect on Experimental Atherosclerosis in hyperlipidemic mice, and only in situations of severe vitamin E deficiency and independent of lipid oxidation in the vessel wall.
