المؤلفون: Soto, Miguel Copaja, Valenzuela, Rodrigo, Saldana, Adiela, Ocaranza, Maria Paz, Jalil, Jorge E., Vio, Carlos, Lijnen, Paul, Ordenes, Gamaliel E., Sanchez, Raul Vivar, Lavandero, Sergio, Diaz-Araya, Guillermo

جغرافية الموضوع: LONDON

الوصف: 4 ; FONDECYT ; 3 ; FONDECYT

العلاقة: instname: Conicyt; reponame: Repositorio Digital RI2.0; info:eu-repo/grantAgreement/Fondecyt/1080590; info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477; https://doi.org/10.1177/1470320308096408Test; 1080590; https://hdl.handle.net/10533/142134Test

الإتاحة: https://doi.org/10.1177/1470320308096408Test
https://hdl.handle.net/10533/142134Test

المؤلفون: Driesen, Ronald B., Nagaraju, Chandan K., Abi-Char, Joëlle, Coenen, Tamara, Lijnen, Paul J., Fagard, Robert H., Sipido, Karin R., Petrov, Victor V.

مصطلحات موضوعية: Original Article

الوصف: Aims Differentiation of cardiac fibroblasts (Fbs) into myofibroblasts (MyoFbs) is responsible for connective tissue build-up in myocardial remodelling. We examined MyoFb differentiation and reversibility. Methods and results Adult rat cardiac Fbs were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different levels of Fb differentiation. Fb spontaneously differentiated to proliferating MyoFb (p-MyoFb) with stress fibre formation decorated with alpha-smooth muscle actin (α-SMA). Transforming growth factor-β1 (TGF-β1) promoted differentiation into α-SMA-positive MyoFb showing near the absence of proliferation, i.e. non-p-MyoFb. SD-208, a TGF-β-receptor-I (TGF-β-RI) kinase blocker, inhibited p-MyoFb differentiation as shown by stress fibre absence, low α-SMA expression, and high proliferation levels. Fb seeded in collagen matrices induced no contraction, whereas p-MyoFb and non-p-MyoFb induced 2.5- and four-fold contraction. Fb produced little collagen but high levels of interleukin-10. Non-p-MyoFb had high collagen production and high monocyte chemoattractant protein-1 and tissue inhibitor of metalloproteinases-1 levels. Transcriptome analysis indicated differential activation of gene networks related to differentiation of MyoFb (e.g. paxilin and PAK) and reduced proliferation of non-p-MyoFb (e.g. cyclins and cell cycle regulation). Dedifferentiation of p-MyoFb with stress fibre de-polymerization, but not of non-p-MyoFb, was induced by SD-208 despite maintained stress. Stress fibre de-polymerization could also be induced by mechanical strain release in p-MyoFb and non-p-MyoFb (2-day cultures in unrestrained 3-D collagen matrices). Only p-MyoFb showed true dedifferentiation after long-term 3-D cultures. Conclusions Fb, p-MyoFb, and non-p-MyoFb have a distinct gene expression, ultrastructural, and functional profile. Both reduction in mechanical strain and TGF-β-RI kinase inhibition can reverse p-MyoFb differentiation but not non-p-MyoFb.

وصف الملف: text/html

العلاقة: http://cardiovascres.oxfordjournals.org/cgi/content/short/cvt338v2Test; http://dx.doi.org/10.1093/cvr/cvt338Test

الإتاحة: https://doi.org/10.1093/cvr/cvt338Test
http://cardiovascres.oxfordjournals.org/cgi/content/short/cvt338v2Test

المؤلفون: Lauwerys, Robert, Amery, Antoon, Bernard, Alfred, Bruaux, Pierre, Buchet, Jean-Pierre, Claeys, Françoise, De Plaen, Pierre, Ducoffre, Geneviève, Fagard, Robert, Lijnen, Paul, Nick, Laurence, Roels, Harry, Rondia, Désiré, Saint-Remy, Annie, Sartor, Francis, Staessen, Jan

المصدر: Environmental Health Perspectives, 1990 Jul 01. 87, 283-289.

الوصول الحر: https://www.jstor.org/stable/3431036Test

المؤلفون: Thijs, Lutgarde, Staessen, Jan, Amery, Antoon, Bruaux, Pierre, Buchet, Jean-Pierre, Claeys, Françoise, De Plaen, Pierre, Ducoffre, Geneviève, Lauwerys, Robert, Lijnen, Paul, Nick, Laurence, Remy, Annie Saint, Roels, Harry, Rondia, Désiré, Sartor, Francis

المصدر: Environmental Health Perspectives, 1992 Nov 01. 98, 251-258.

الوصول الحر: https://www.jstor.org/stable/3431279Test

المؤلفون: Driesen, Ronald B., Nagaraju, Chandan K., Abi-Char, Joëlle, Coenen, Tamara, Lijnen, Paul J., Fagard, Robert H., Sipido, Karin R., Petrov, Victor V.

مصطلحات موضوعية: Original Article

الوصف: Aim Differentiation of cardiac fibroblasts (Fb) into myofibroblasts (MyoFb) is responsible for connective tissue buildup in myocardial remodeling. We examined MyoFb differentiation and reversibility. Methods and Results Adult rat cardiac Fb were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different levels of Fb differentiation. Fb spontaneously differentiated to proliferating MyoFb (p-MyoFb) with stress fiber formation decorated with alpha-smooth muscle actin (α-SMA). Transforming growth factor-β1 (TGF-β1) promoted differentiation into α-SMA positive MyoFb showing near absence of proliferation i.e. non-p-MyoFb. SD-208, a TGF-β-receptor-I kinase blocker, inhibited p-MyoFb differentiation as shown by stress fiber absence, low α-SMA expression, and high proliferation levels. Fb seeded in collagen matrices induced no contraction, whereas p-MyoFb and non-p-MyoFb induced 2.5- and 4-fold contraction. Fb produced little collagen but high levels of IL-10. Non-p-MyoFb had high collagen production and high MCP-1 and TIMP-1 levels. Transcriptome analysis indicated differential activation of gene networks related to differentiation of MyoFb (e.g. paxilin, PAK) and reduced proliferation of non-p-MyoFb (e.g. cyclins and cell cycle regulation). Dedifferentiation of p-MyoFb with stress fiber de-polymerization, but not of non-p-MyoFb, was induced by SD-208 despite maintained stress. Stress fiber de-polymerization could also be induced by mechanical strain release in p-MyoFb and non-p-MyoFb (2 day culture in unrestrained 3-D collagen matrices). Only p-MyoFb showed true dedifferentiation after long-term 3-D culture. Conclusions Fb, p-MyoFb and non-p-MyoFb have a distinct gene expression, ultrastructural and functional profile. Both reduction in mechanical strain and TGF-β-receptor-I kinase inhibition can reverse p-MyoFb differentiation but not of non-p-MyoFb.

وصف الملف: text/html

العلاقة: http://cardiovascres.oxfordjournals.org/cgi/content/short/cvt338v1Test; http://dx.doi.org/10.1093/cvr/cvt338Test

الإتاحة: https://doi.org/10.1093/cvr/cvt338Test
http://cardiovascres.oxfordjournals.org/cgi/content/short/cvt338v1Test

المؤلفون: Lijnen, Paul J., van Pelt, Jos F., Fagard, Robert H.

المصدر: Cardiovascular Therapeutics ; volume 30, issue 1 ; ISSN 1755-5914 1755-5922

الوصف: SUMMARY Superoxide anion generated by NAD(P)H‐oxidase has an important role in the pathogenesis of cardiovascular diseases and scavenging superoxide anion can be considered as a reasonable therapeutic strategy. In hypertensive heart diseases there is a mutual reinforcement of reactive oxygen species (ROS) and angiotensin II (ANG II). ANG II increases the NAD(P)H‐dependent superoxide anion production and the intracellular generation of ROS in cardiac fibroblasts and apocynin, a membrane NAD(P)H oxidase inhibitor, abrogates this rise. ANG II also stimulates the collagen production, the collagen I and III content and mRNA expression in cardiac fibroblasts and apocynin abolishes this induction. In this review we demonstrate that scavenging superoxide anion by tempol or EUK‐8 or administration of PEG‐superoxide dismutase (SOD) inhibits collagen production in cardiac fibroblasts. On the contrary increasing superoxide anion formation by inhibition of SOD stimulates collagen production. A vital role of SOD and the generated ROS can be suggested in the regulation and organization of collagen in cardiac fibroblasts. Specific pharmacological intervention with SOD mimetics can probably be an alternative approach for reducing myocardial fibrosis.

الإتاحة: https://doi.org/10.1111/j.1755-5922.2010.00205.xTest

المؤلفون: Lijnen, Paul J.

المصدر: The Open Hypertension Journal ; volume 4, issue 1, page 1-17 ; ISSN 1876-5262

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine

الإتاحة: https://doi.org/10.2174/1876526201104010001Test

المؤلفون: Lijnen, Paul J., van Pelt, Jos F., Fagard, Robert H.

مصطلحات موضوعية: Original Contributions

الوصف: Background The aim of this study was to determine whether angiotensin II (ANG II) affects the protein and mRNA expressions of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD) in cardiac fibroblasts of rats through inducing the phosphorylation of the proteins Akt and FOXO3a, thereby contributing to the oxidative stress in the myocardium. Methods Cardiac fibroblasts (passage 2) from normal male adult rats were cultured to confluency and incubated in serum-free Dulbecco's modified Eagle's medium for 24h. The cells were then preincubated with/without the tested inhibitors for 1h and then further incubated with/without ANG II (1µmol/l) for 24h. Results ANG II increased the production of superoxide ions in the cardiac fibroblasts, and decreased the activity levels of both Mn-SOD and CuZn-SOD, but not the activity levels of catalase and glutathione peroxidase. ANG II also decreased the mRNA and protein expressions of Mn-SOD, but not those of CuZn-SOD, catalase, and glutathione peroxidase. The likely mechanism through which ANG II produces the effect of reducing Mn-SOD activity is by reducing the extent of binding of FOXO3a to the Mn-SOD promoter. In control fibroblasts, inhibition of FOXO3a transcription with small-interfering RNA (siRNA) led to a reduction in the binding of FOXO3a to the Mn-SOD promoter, and a concomitant reduction in Mn-SOD gene expression. Our data suggest that when Akt is phosphorylated by ANG II, P-Akt is translocated from the cytoplasm to the nucleus; subsequently, nuclear phosphorylation of FOXO3a by P-Akt leads to relocalization of FOXO3a from the nucleus to the cytosol, resulting in a decrease in its transcriptional activity, and consequently in Mn-SOD expression. The likelihood of such a mechanism of action is further strengthened by the fact that inhibition of phosphoinositide 3-kinase with wortmannin or LY 294002, and Akt inhibition, were shown to lead to a decrease in P-AKT and to a consequent increase in Mn-SOD mRNA expression. Conclusions Our data indicate that ANG ...

وصف الملف: text/html

العلاقة: http://ajh.oxfordjournals.org/cgi/content/short/23/10/1128Test; http://dx.doi.org/10.1038/ajh.2010.128Test

الإتاحة: https://doi.org/10.1038/ajh.2010.128Test
http://ajh.oxfordjournals.org/cgi/content/short/23/10/1128Test

المؤلفون: Lijnen, Paul J.

مصطلحات موضوعية: News and Views

وصف الملف: text/html

العلاقة: http://ajh.oxfordjournals.org/cgi/content/short/22/1/8Test; http://dx.doi.org/10.1038/ajh.2008.328Test

الإتاحة: https://doi.org/10.1038/ajh.2008.328Test
http://ajh.oxfordjournals.org/cgi/content/short/22/1/8Test

المؤلفون: Lijnen, Paul, Petrov, Victor, van Pelt, Jos, Fagard, Robert

مصطلحات موضوعية: Original Contributions

الوصف: Background The aim of this study was to determine whether inhibition of superoxide dismutase (SOD) with diethyldithiocarbamic acid (DETC) could affect the collagen production, the mRNA and protein expression of collagen types I and III, and fibronectin in control and angiotensin II (ANG II)-treated cardiac fibroblasts. Its effect was compared with the SOD mimetics tempol and EUK-8 and with polyethyleneglycol (PEG)-SOD. Methods Cardiac fibroblasts were cultured to confluence, incubated in serum-free Dulbecco's modified Eagle's medium for 24 h, preincubated with(out) the tested inhibitors for 1 h and further incubated with(out) ANG II (1 µmol/l) for 24 h. Results DETC dose-dependently inhibited the activity of CuZn-SOD in cardiac fibroblasts. Superoxide anion production was increased by DETC and decreased by tempol in control and ANG II–treated fibroblasts. DETC also reduced the intracellular generation of reactive oxygen species (ROS) (such as H 2 O 2 , hydroxyl radicals, hydroperoxides) in control and ANG II–treated fibroblasts, whereas tempol reduced the ROS production only in ANG II–treated fibroblasts. ANG II and DETC stimulated the collagen production and the collagen I and fibronectin content in fibroblasts. The SOD mimetics tempol and EUK-8 as well as PEG-SOD reduced the collagen production. ANG II and DETC stimulated the tissue inhibitor of metalloproteinase–1 (TIMP-1) and TIMP-2 levels, whereas tempol decreased the TIMP-2 content in control and ANG II–treated fibroblasts. Matrix metalloproteinase (MMP)-1 level was reduced by ANG II and DETC and increased by tempol. Conclusion These data suggest a vital role of SOD and the formed ROS in the accumulation of collagen in cardiac fibroblasts.

وصف الملف: text/html

العلاقة: http://ajh.oxfordjournals.org/cgi/content/short/21/10/1129Test; http://dx.doi.org/10.1038/ajh.2008.242Test

الإتاحة: https://doi.org/10.1038/ajh.2008.242Test
http://ajh.oxfordjournals.org/cgi/content/short/21/10/1129Test