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5. Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway

Author

Jm, Alberto, Hamelet, J., Noll, C., Blaise, S., Jp, Bronowicki, Jl, Guéant, Jm, Delabar, Janel, N., Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)

Subjects
ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

7. Oral abstract presentations

Author

Pereira, L., primary, Ruiz-Hurtado, G., additional, Morel, E., additional, Dominguez, A., additional, Benitah, J. P., additional, Bers, D. M., additional, Lezoualc'h, F., additional, Gomez, A., additional, Collins, T. P., additional, Sikkel, M. B., additional, O' Gara, P., additional, Lyon, A. R., additional, Harding, S. E., additional, Macleod, K. T., additional, Wantha, S., additional, Alard, J. E., additional, Doering, Y., additional, Drechsler, M., additional, Megens, R. T., additional, Hackeng, T., additional, Weber, C., additional, Soehnlein, O., additional, Dietel, B., additional, Cicha, I., additional, Altendorf, R., additional, Daniel, W. G., additional, Garlichs, C. D., additional, Mukherjee, U., additional, Ong, S. B., additional, Davidson, S. M., additional, Szabadkai, G., additional, Yellon, D. M., additional, Hausenloy, D. J., additional, Neary, M. T., additional, Hall, A. R., additional, Hirst, E., additional, Mohun, T. J., additional, Breckenridge, R. A., additional, Akhmedov, A., additional, Camici, G. G., additional, Stivala, S., additional, Holy, E. W., additional, Breitenstein, A., additional, Lohmann, C., additional, Beer, J.-H., additional, Tanner, F. C., additional, Matter, C. M., additional, Luescher, T. F., additional, Hulsmans, M., additional, Geeraert, B., additional, Arnould, T., additional, Tsatsanis, C., additional, Holvoet, P., additional, Hermida, N., additional, Markl, A., additional, Hamelet, J., additional, Herijgers, P., additional, Horman, S., additional, Noppe, G., additional, Beauloye, C., additional, Van Bilsen, M., additional, Dessy, C., additional, Balligand, J.-L., additional, Del Giorno, R., additional, Moreno Velasquez, I., additional, Leander, K., additional, Frumento, P., additional, Vikstrom, M., additional, Pirro, M., additional, Mannarino, M. R., additional, Mannarino, E., additional, De Faire, U., additional, Gigante, B., additional, Chaudhry, B., additional, Chrystal, P., additional, Henderson, D. J., additional, Fulcoli, F. G., additional, Chen, L., additional, Martucciello, S., additional, Illingworth, E., additional, Baldini, A., additional, Mavroidis, M., additional, Davos, C., additional, Psarras, S., additional, Varela, A., additional, Kostavasili, I., additional, Capetanaki, Y., additional, Engstrom Klarstrom, K., additional, Skoglund, C., additional, Kalvegren, H., additional, Bengtsson, T., additional, Drawnel, F., additional, Wachten, D., additional, Molkentin, J. D., additional, Sjaastad, I., additional, Liu, N., additional, Mikoshiba, K., additional, Bootman, M. D., additional, Roderick, H. L., additional, Di Gregoli, K., additional, Salter, R., additional, and Johnson, J. L., additional

Published
2012
Full Text
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8. Sunday, 18 July 2010

Author

Schuchardt, M., primary, Toelle, M., additional, Huang, T., additional, Wiedon, A., additional, Van Der Giet, M., additional, Mill, C., additional, George, S., additional, Jeremy, J., additional, Santulli, G., additional, Illario, M., additional, Cipolletta, E., additional, Sorriento, D., additional, Del Giudice, C., additional, Anastasio, A., additional, Trimarco, B., additional, Iaccarino, G., additional, Jobs, A., additional, Wagner, C., additional, Kurtz, A., additional, De Wit, C., additional, Koller, A., additional, Suvorava, T., additional, Weber, M., additional, Dao, V., additional, Kojda, G., additional, Tsaousi, A., additional, Lyon, C., additional, Williams, H., additional, Barth, N., additional, Loot, A., additional, Fleming, I., additional, Keul, P., additional, Lucke, S., additional, Graeler, M., additional, Heusch, G., additional, Levkau, B., additional, Biessen, E., additional, De Jager, S., additional, Bermudez-Pulgarin, B., additional, Bot, I., additional, Abia, R., additional, Van Berkel, T., additional, Renger, A., additional, Noack, C., additional, Zafiriou, M., additional, Dietz, R., additional, Bergmann, M., additional, Zelarayan, L., additional, Hammond, J., additional, Hamelet, J., additional, Van Assche, T., additional, Belge, C., additional, Vanderper, A., additional, Langin, D., additional, Herijgers, P., additional, Balligand, J., additional, Perrot, A., additional, Neubert, M., additional, Posch, M., additional, Oezcelik, C., additional, Waldmuller, S., additional, Berger, F., additional, Scheffold, T., additional, Bouvagnet, P., additional, Ozcelik, C., additional, Lebreiro, A., additional, Martins, E., additional, Lourenco, P., additional, Cruz, C., additional, Martins, M., additional, Bettencourt, P., additional, Maciel, M., additional, Abreu-Lima, C., additional, Pilichou, K., additional, Bauce, B., additional, Rampazzo, A., additional, Carturan, E., additional, Corrado, D., additional, Thiene, G., additional, Basso, C., additional, Piccini, I., additional, Fortmueller, L., additional, Kuhlmann, M., additional, Schaefers, M., additional, Carmeliet, P., additional, Kirchhof, P., additional, Fabritz, L., additional, Sanchez, J., additional, Rodriguez-Sinovas, A., additional, Agullo, E., additional, Garcia-Dorado, D., additional, Lymperopoulos, A., additional, Rengo, G., additional, Gao, E., additional, Zincarelli, C., additional, Koch, W., additional, Morgan, P., additional, Diez, A., additional, Perez, N., additional, Cingolani, H., additional, Zahradnikova, A., additional, Polakova, E., additional, Zahradnik, I., additional, Fluschnik, N., additional, Sossalla, S., additional, Ort, K., additional, Neef, S., additional, Hasenfuss, G., additional, Maier, L., additional, Weinert, S., additional, Poitz, D., additional, Herold, J., additional, Schmeisser, A., additional, Strasser, J., additional, Braun-Dullaeus, R., additional, Nazari-Jahantigh, M., additional, Weber, C., additional, Schober, A., additional, Leuner, A., additional, Eichhorn, B., additional, Ravens, U., additional, Morawietz, H., additional, Babes, E., additional, Babes, V., additional, Popescu, M., additional, Ardelean, A., additional, Rus, M., additional, Bustea, C., additional, Gwozdz, P., additional, Csanyi, G., additional, Luzak, B., additional, Gajda, M., additional, Mateuszuk, L., additional, Chmura-Skirlinska, A., additional, Watala, C., additional, Chlopicki, S., additional, Kierzkowska, I., additional, Sulicka, J., additional, Kwater, A., additional, Strach, M., additional, Surdacki, A., additional, Siedlar, M., additional, Grodzicki, T., additional, Olieslagers, S., additional, Pardali, L., additional, Tchaikovski, V., additional, Ten Dijke, P., additional, Waltenberger, J., additional, Renner, M., additional, Redwan, B., additional, Winter, M., additional, Panzenboeck, A., additional, Jakowitsch, J., additional, Sadushi-Kolici, R., additional, Bonderman, D., additional, Lang, I., additional, Toso, A., additional, Tanini, L., additional, Pizzetti, T., additional, Leoncini, M., additional, Maioli, M., additional, Tedeschi, D., additional, Oliviero, C., additional, Bellandi, F., additional, Casprini, P., additional, Amato, M., additional, Molins, B., additional, Pena, E., additional, Badimon, L., additional, Ferreiro Gutierrez, J., additional, Ueno, M., additional, Alissa, R., additional, Dharmashankar, K., additional, Capodanno, D., additional, Desai, B., additional, Bass, T., additional, Angiolillo, D., additional, Chabielska, E., additional, Gromotowicz, A., additional, Szemraj, J., additional, Stankiewicz, A., additional, Zakrzeska, A., additional, Mohammed, S., additional, Molla, F., additional, Soldo, A., additional, Russo, I., additional, Germano, G., additional, Balconi, G., additional, Staszewsky, L., additional, Latini, R., additional, Lynch, F., additional, Austin, C., additional, Prendergast, B., additional, Keenan, D., additional, Malik, R., additional, Izzard, A., additional, Heagerty, A., additional, Czikora, A., additional, Lizanecz, E., additional, Rutkai, I., additional, Boczan, J., additional, Porszasz, R., additional, Papp, Z., additional, Edes, I., additional, Toth, A., additional, Colantuoni, A., additional, Vagnani, S., additional, Lapi, D., additional, Maroz-Vadalazhskaya, N., additional, Koslov, I., additional, Shumavetz, V., additional, Glibovskaya, T., additional, Ostrovskiy, Y., additional, Koutsiaris, A., additional, Tachmitzi, S., additional, Kotoula, M., additional, Giannoukas, A., additional, Tsironi, E., additional, Darago, A., additional, Orosz, P., additional, Megyesi, Z., additional, Schudeja, S., additional, Matschke, K., additional, Deussen, A., additional, Castro, M., additional, Cena, J., additional, Walsh, M., additional, Schulz, R., additional, Poddar, K., additional, Rha, S., additional, Ramasamy, S., additional, Park, J., additional, Choi, C., additional, Seo, H., additional, Park, C., additional, Oh, D., additional, Almeida, J., additional, Pimenta, S., additional, Bernardes, J., additional, Machado, J., additional, Sabatasso, S., additional, Laissue, J., additional, Hlushchuk, R., additional, Brauer-Krisch, E., additional, Bravin, A., additional, Blattmann, H., additional, Michaud, K., additional, Djonov, V., additional, Hirschberg, K., additional, Tarcea, V., additional, Pali, S., additional, Korkmaz, S., additional, Loganathan, S., additional, Merkely, B., additional, Karck, M., additional, Szabo, G., additional, Pagliani, L., additional, Faggin, E., additional, Rattazzi, M., additional, Puato, M., additional, Presta, M., additional, Grego, F., additional, Deriu, G., additional, Pauletto, P., additional, Kaiser, R., additional, Albrecht, K., additional, Schgoer, W., additional, Theurl, M., additional, Beer, A., additional, Wiedemann, D., additional, Steger, C., additional, Bonaros, N., additional, Kirchmair, R., additional, Kharlamov, A., additional, Cabaravdic, M., additional, Breuss, J., additional, Uhrin, P., additional, Binder, B., additional, Fiordaliso, F., additional, Maggioni, M., additional, Biondi, A., additional, Masson, S., additional, Cervo, L., additional, Francke, A., additional, Soenke, W., additional, Strasser, R., additional, Hecht, N., additional, Vajkoczy, P., additional, Woitzik, J., additional, Hackbusch, D., additional, Gatzke, N., additional, Duelsner, A., additional, Tsuprykov, O., additional, Slavic, S., additional, Buschmann, I., additional, Kappert, K., additional, Massaro, M., additional, Scoditti, E., additional, Carluccio, M., additional, Storelli, C., additional, Distante, A., additional, De Caterina, R., additional, Barandi, L., additional, Harmati, G., additional, Simko, J., additional, Horvath, B., additional, Szentandrassy, N., additional, Banyasz, T., additional, Magyar, J., additional, Nanasi, P., additional, Kaya, A., additional, Uzunhasan, I., additional, Yildiz, A., additional, Yigit, Z., additional, Turkoglu, C., additional, Doisne, N., additional, Zannad, N., additional, Hivert, B., additional, Cosnay, P., additional, Maupoil, V., additional, Findlay, I., additional, Virag, L., additional, Kristof, A., additional, Koncz, I., additional, Szel, T., additional, Jost, N., additional, Biliczki, P., additional, Papp, J., additional, Varro, A., additional, Bukowska, A., additional, Skopp, K., additional, Hammwoehner, M., additional, Huth, C., additional, Bode-Boeger, S., additional, Goette, A., additional, Workman, A., additional, Dempster, J., additional, Marshall, G., additional, Rankin, A., additional, Revnic, C., additional, Ginghina, C., additional, Revnic, F., additional, Yakushev, S., additional, Petrushanko, I., additional, Makhro, A., additional, Segato Komniski, M., additional, Mitkevich, V., additional, Makarov, A., additional, Gassmann, M., additional, Bogdanova, A., additional, Rutkovskiy, A., additional, Mariero, L., additional, Stenslokken, K., additional, Valen, G., additional, Vaage, J., additional, Dizayee, S., additional, Kaestner, S., additional, Kuck, F., additional, Piekorz, R., additional, Hein, P., additional, Matthes, J., additional, Nurnberg, B., additional, Herzig, S., additional, Hertel, F., additional, Switalski, A., additional, Bender, K., additional, Kienitz, M.-C., additional, Pott, L., additional, Fornai, L., additional, Angelini, A., additional, Erika Amstalden Van Hove, E., additional, Fedrigo, M., additional, Heeren, R., additional, Kruse, M., additional, Pongs, O., additional, Lehmann, H., additional, Martens-Lobenhoffer, J., additional, Roehl, F., additional, Radicke, S., additional, Cotella, C., additional, Sblattero, D., additional, Schaefer, M., additional, Wettwer, E., additional, Santoro, C., additional, Seyler, C., additional, Kulzer, M., additional, Zitron, E., additional, Scholz, E., additional, Welke, F., additional, Thomas, D., additional, Karle, C., additional, Schmidt, K., additional, Dobrev, D., additional, Houshmand, N., additional, Menesi, D., additional, Cotella, D., additional, Szuts, V., additional, Puskas, L., additional, Kiss, I., additional, Deak, F., additional, Tereshchenko, S., additional, Gladyshev, M., additional, Kalachova, G., additional, Syshchik, N., additional, Gogolashvili, N., additional, Dedok, E., additional, Evert, L., additional, Wenzel, J., additional, Brandenburger, M., additional, Bogdan, R., additional, Richardt, D., additional, Reppel, M., additional, Hescheler, J., additional, Dendorfer, A., additional, Terlau, H., additional, Wiegerinck, R., additional, Galvez-Monton, C., additional, Jorge, E., additional, Martinez, R., additional, Ricart, E., additional, Cinca, J., additional, Bagavananthem Andavan, G., additional, Lemmens Gruber, R., additional, Brack, K., additional, Coote, J., additional, Ng, G., additional, Daimi, H., additional, Haj Khelil, A., additional, Neji, A., additional, Ben Hamda, K., additional, Maaoui, S., additional, Aranega, A., additional, Chibani, J., additional, Franco Jaime, D., additional, Tanko, A.-S., additional, Daniel, J.-M., additional, Bielenberg, W., additional, Stieger, P., additional, Tillmanns, H., additional, Sedding, D., additional, Fortini, C., additional, Toffoletto, B., additional, Fucili, A., additional, Beltrami, A., additional, Fiorelli, V., additional, Francolini, G., additional, Ferrari, R., additional, Beltrami, C., additional, Castellani, C., additional, Ravara, B., additional, Tavano, R., additional, Vettor, R., additional, De Coppi, P., additional, Papini, E., additional, Gunetti, M., additional, Fagioli, F., additional, Suffredini, S., additional, Sartiani, L., additional, Stillitano, F., additional, Mugelli, A., additional, Cerbai, E., additional, Krausgrill, B., additional, Halbach, M., additional, Soemantri, S., additional, Schenk, K., additional, Lange, N., additional, Saric, T., additional, Muller-Ehmsen, J., additional, Kavanagh, D., additional, Zhao, Y., additional, Yemm, A., additional, Kalia, N., additional, Wright, E., additional, Farrell, K., additional, Wallrapp, C., additional, Geigle, P., additional, Lewis, A., additional, Stratford, P., additional, Malik, N., additional, Holt, C., additional, Raths, M., additional, Zagallo, M., additional, Luni, C., additional, Serena, E., additional, Cimetta, E., additional, Zatti, S., additional, Giobbe, G., additional, Elvassore, N., additional, Zaglia, T., additional, Zambon, A., additional, Gordon, K., additional, Mioulane, M., additional, Foldes, G., additional, Ali, N., additional, Harding, S., additional, Gorbe, A., additional, Szunyog, A., additional, Varga, Z., additional, Pirity, M., additional, Rungaruniert, S., additional, Dinnyes, A., additional, Csont, T., additional, Ferdinandy, P., additional, Iqbal, A., additional, Schneider, M. D., additional, Khodjaeva, E., additional, Ibadov, R., additional, Khalikulov, K., additional, Mansurov, A., additional, Astvatsatryan, A., additional, Senan, M., additional, Nemeth, A., additional, Lenkey, Z., additional, Ajtay, Z., additional, Cziraki, A., additional, Sulyok, E., additional, Horvath, I., additional, Lobenhoffer, J., additional, Bode-Boger, S., additional, Li, J., additional, He, Y., additional, Yang, X., additional, Wang, F., additional, Xu, H., additional, Li, X., additional, Zhao, X., additional, Lin, Y., additional, Juszynski, M., additional, Ciszek, B., additional, Jablonska, A., additional, Stachurska, E., additional, Ratajska, A., additional, Atkinson, A., additional, Inada, S., additional, Sleiman, R., additional, Zhang, H., additional, Boyett, M., additional, Dobrzynski, H., additional, Fedorenko, O., additional, Hao, G., additional, Yanni, J., additional, Buckley, D., additional, Anderson, R., additional, Ma, Y., additional, Ma, X., additional, Hu, Y., additional, Yang, Y., additional, Huang, D., additional, Liu, F., additional, Huang, Y., additional, Liu, C., additional, Jedrzejczyk, T., additional, Balwicki, L., additional, Wierucki, L., additional, Zdrojewski, T., additional, Agarkova, I., additional, Vogel, J., additional, Korybalska, K., additional, Pyda, M., additional, Witowski, J., additional, Ibatov, A., additional, Sozmen, N., additional, Seymen, A., additional, Tuncay, E., additional, Turan, B., additional, Chen, B., additional, Houston-Feenstra, L., additional, Chiong, J. R., additional, Jutzy, K., additional, Furundzija, V., additional, Kaufmann, J., additional, Meyborg, H., additional, Fleck, E., additional, Stawowy, P., additional, Ksiezycka-Majczynska, E., additional, Lubiszewska, B., additional, Kruk, M., additional, Kurjata, P., additional, Ruzyllo, W., additional, Driesen, R., additional, Coenen, T., additional, Fagard, R., additional, Sipido, K., additional, Petrov, V., additional, Aksentijevic, D., additional, Lygate, C., additional, Makinen, K., additional, Sebag-Montefiore, L., additional, Medway, D., additional, Schneider, J., additional, Neubauer, S., additional, Gasser, R., additional, Holzwart, E., additional, Rainer, P., additional, Von Lewinski, D., additional, Maechler, H., additional, Gasser, S., additional, Roessl, U., additional, Pieske, B., additional, Krueger, J., additional, Kintscher, U., additional, Podramagi, T., additional, Paju, K., additional, Piirsoo, A., additional, Roosimaa, M., additional, Kadaja, L., additional, Orlova, E., additional, Ruusalepp, A., additional, Seppet, E., additional, Auquier, J., additional, Ginion, A., additional, Hue, L., additional, Horman, S., additional, Beauloye, C., additional, Vanoverschelde, J., additional, Bertrand, L., additional, Fekete, V., additional, Zvara, A., additional, Pipis, J., additional, Konya, C., additional, Csonka, C., additional, Kraigher-Krainer, E., additional, Von Lewinksi, D., additional, Gonzalez-Loyola, A., additional, Barba, I., additional, Fernandez-Sanz, C., additional, Ruiz-Meana, M., additional, Forteza, M., additional, Bodi Peris, V., additional, Monleon, D., additional, Mainar, L., additional, Morales, J., additional, Moratal, D., additional, Trapero, I., additional, Chorro, F., additional, Leszek, P., additional, Sochanowicz, B., additional, Szperl, M., additional, Kolsut, P., additional, Piotrowski, W., additional, Rywik, T., additional, Danko, B., additional, Kruszewski, M., additional, Stanley, W., additional, Khairallah, R., additional, Khanna, N., additional, O'shea, K., additional, Kristian, T., additional, Hecker, P., additional, Des Rosiers, R., additional, Fiskum, G., additional, Fernandez-Alfonso, M., additional, Guzman-Ruiz, R., additional, Somoza, B., additional, Gil-Ortega, M., additional, Attane, C., additional, Castan-Laurell, I., additional, Valet, P., additional, Ruiz-Gayo, M., additional, Denissevich, T., additional, Schrepper, A., additional, Schwarzer, M., additional, Amorim, P., additional, Schoepe, M., additional, Mohr, F., additional, Doenst, T., additional, Chiellini, G., additional, Ghelardoni, S., additional, Saba, A., additional, Marchini, M., additional, Frascarelli, S., additional, Raffaelli, A., additional, Scanlan, T., additional, Zucchi, R., additional, Van Den Akker, N., additional, Molin, D., additional, Kolk, F., additional, Jeukens, F., additional, Olde Engberink, R., additional, Post, M., additional, Verbruggen, S., additional, Schulten, H., additional, Rochais, F., additional, Kelly, R., additional, Aberg, M., additional, Johnell, M., additional, Wickstrom, M., additional, Siegbahn, A., additional, Dimitrakis, P., additional, Groppalli, V., additional, Ott, D., additional, Seifriz, F., additional, Suter, T., additional, Zuppinger, C., additional, Kashcheyeu, Y., additional, Mueller, R., additional, Wiesen, M., additional, Gruendemann, D., additional, Falcao-Pires, I., additional, Fontes-Sousa, A., additional, Lopes-Conceicao, L., additional, Bras-Silva, C., additional, Leite-Moreira, A., additional, Bukauskas, F., additional, Palacios-Prado, N., additional, Norheim, F., additional, Raastad, T., additional, Thiede, B., additional, Drevon, C., additional, Haugen, F., additional, Lindner, D., additional, Westermann, D., additional, Zietsch, C., additional, Schultheiss, H.-P., additional, Tschoepe, C., additional, Horn, M., additional, Graham, H., additional, Hall, M., additional, Richards, M., additional, Clarke, J., additional, Dibb, K., additional, Trafford, A., additional, Cheng, C.-F., additional, Lin, H., additional, Eigeldiger-Berthou, S., additional, Buntschu, P., additional, Frobert, A., additional, Flueck, M., additional, Tevaearai, H., additional, Kadner, A., additional, Mikhailov, A., additional, Torrado, M., additional, Centeno, A., additional, Lopez, E., additional, Lourido, L., additional, Castro Beiras, A., additional, Popov, T., additional, Srdanovic, I., additional, Petrovic, M., additional, Canji, T., additional, Kovacevic, M., additional, Jovelic, A., additional, Sladojevic, M., additional, Panic, G., additional, Kararigas, G., additional, Fliegner, D., additional, Regitz-Zagrosek, V., additional, De La Rosa Sanchez, A., additional, Dominguez, J., additional, Sedmera, D., additional, Franco, D., additional, Medunjanin, S., additional, Burgbacher, F., additional, Han, W., additional, Zhang, J., additional, Gao, X., additional, Bayliss, C., additional, Song, W., additional, Stuckey, D., additional, Dyer, E., additional, Leung, M.-C., additional, Monserrat, L., additional, Marston, S., additional, Fusco, A., additional, Paillard, M., additional, Liang, J., additional, Strub, G., additional, Gomez, L., additional, Hait, N., additional, Allegood, J., additional, Lesnefsky, E., additional, Spiegel, S., additional, Zuchi, C., additional, Coiro, S., additional, Bettini, M., additional, Ciliberti, G., additional, Mancini, I., additional, Tritto, I., additional, Becker, L., additional, Ambrosio, G., additional, Adam, T., additional, Sharp, S., additional, Opie, L., additional, Lecour, S., additional, Khaliulin, I., additional, Parker, J., additional, Halestrap, A., additional, Kandasamy, A., additional, Osterholt, M., additional, Miro-Casas, E., additional, Boengler, K., additional, Menazza, S., additional, Canton, M., additional, Sheeran, F., additional, Di Lisa, F., additional, Pepe, S., additional, Borchi, E., additional, Manni, M., additional, Bargelli, V., additional, Giordano, C., additional, D'amati, G., additional, Nediani, C., additional, Raimondi, L., additional, Micova, P., additional, Balkova, P., additional, Kolar, F., additional, Neckar, J., additional, Novak, F., additional, Novakova, O., additional, Schuchardt, M., additional, Pruefer, N., additional, Pruefer, J., additional, Jankowski, V., additional, Jankowski, J., additional, Su, Y., additional, Zervou, S., additional, Seidel, B., additional, Radovits, T., additional, Barnucz, E., additional, Aggeli, I., additional, Kefaloyianni, E., additional, Beis, I., additional, Gaitanaki, C., additional, Lacerda, L., additional, Somers, S., additional, Paur, H., additional, Nikolaev, V., additional, Lyon, A., additional, Silva, S., additional, Gomes, M., additional, Ferreira, P., additional, Capuano, V., additional, Ferron, L., additional, Ruchon, Y., additional, Ben Mohamed, F., additional, Renaud, J.-F., additional, Goncalves, N., additional, Gavina, C., additional, Pinho, S., additional, Moura, C., additional, Amorim, M., additional, Pinho, P., additional, Christ, T., additional, Molenaar, P., additional, Kaumann, A., additional, Kletsiou, E., additional, Giannakopoulou, M., additional, Bozas, E., additional, Iliodromitis, E., additional, Anastasiou-Nana, M., additional, Papathanassoglou, E., additional, Chottova Dvorakova, M., additional, Mistrova, E., additional, Slavikova, J., additional, Hynie, S., additional, Sida, P., additional, Klenerova, V., additional, Zakrzewicz, A., additional, Hoffmann, C., additional, Hohberg, M., additional, Chlench, S., additional, Maroski, J., additional, Drab, M., additional, Siegel, G., additional, Pries, A., additional, Schrot, G., additional, Wilck, N., additional, Fechner, M., additional, Arias, A., additional, Meiners, S., additional, Baumann, G., additional, Stangl, V., additional, Stangl, K., additional, Ludwig, A., additional, Christ, A., additional, Eijgelaar, W., additional, Daemen, M., additional, Penfold, M., additional, Schall, T., additional, Hintenberger, R., additional, Kaun, C., additional, Pfaffenberger, S., additional, Maurer, G., additional, Huber, K., additional, Wojta, J., additional, Demyanets, S., additional, Titov, V., additional, Chin-Dusting, J., additional, Vaisman, B., additional, Khong, S., additional, Remaley, A., additional, Andrews, K., additional, Hoeper, A., additional, Khalid, A., additional, Fuglested, B., additional, Aasum, E., additional, Larsen, T., additional, Diebold, I., additional, Petry, A., additional, Djordjevic, T., additional, Belaiba, R., additional, Fratz, S., additional, Hess, J., additional, Kietzmann, T., additional, Goerlach, A., additional, Chess, D., additional, Walsh, K., additional, Van Der Velden, J., additional, Moreira-Goncalves, D., additional, Paulus, W., additional, Niessen, H., additional, Perlini, S., additional, Azibani, F., additional, Tournoux, F., additional, Fazal, L., additional, Polidano, E., additional, Merval, R., additional, Chatziantoniou, C., additional, Samuel, J., additional, Delcayre, C., additional, Mgandela, P., additional, Brooksbank, R., additional, Maswanganyi, T., additional, Woodiwiss, A., additional, Norton, G., additional, Makaula, S., additional, Bucciantini, M., additional, Spinelli, V., additional, Coppini, R., additional, Russo, E., additional, Stefani, M., additional, Sukumaran, V., additional, Watanabe, K., additional, Ma, M., additional, Thandavarayan, R., additional, Azrozal, W., additional, Sari, F., additional, Shimazaki, H., additional, Kobayashi, Y., additional, Roleder, T., additional, Golba, K., additional, Deja, M., additional, Malinowski, M., additional, Wos, S., additional, Grebe, M., additional, Preissner, K., additional, Ercan, E., additional, Guven, A., additional, Asgun, F., additional, Ickin, M., additional, Ercan, F., additional, Kaplan, A., additional, Yavuz, O., additional, Bagla, S., additional, Kuka, J., additional, Vilskersts, R., additional, Vavers, E., additional, Liepins, E., additional, Dambrova, M., additional, Duerr, G., additional, Suchan, G., additional, Heuft, T., additional, Klaas, T., additional, Zimmer, A., additional, Welz, A., additional, Fleischmann, B., additional, Dewald, O., additional, Voelkl, J., additional, Haubner, B., additional, Kremser, C., additional, Mayr, A., additional, Klug, G., additional, Reiner, M., additional, Pachinger, O., additional, Metzler, B., additional, Pisarenko, O., additional, Shulzhenko, V., additional, Pelogeykina, Y., additional, Khatri, D., additional, Studneva, I., additional, Bencsik, P., additional, Kocsis, G., additional, Shamloo, M., additional, Woodburn, K., additional, Szucs, G., additional, Kupai, K., additional, Csont, C., additional, Kocsisne Fodor, G., additional, Monostori, P., additional, and Turi, S., additional

Published
2010
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9. 309 Protection from cardiac fibrosis is induced by beta3 adrenergic receptor in cardiac myocyte through inhibition of paracrine signalling to fibroblast : proteomic analysis of the myocyte secretome.

Author

Hermida, N, Dubois-Deruy, E, Hammond, J, Hamelet, J, Markl, A, Mayr, M, and Balligand, JL

Subjects
HEART fibrosis, ADRENERGIC receptors, MUSCLE cells, CELLULAR signal transduction, HYPERTROPHY, CELL proliferation
Abstract

Background: Cardiac fibrosis is an integral part of myocardial remodelling in response to stress. Mice with cardiac myocyte-specific overexpression of beta3-adrenergic receptor (β3-AR) are protected not only from the development of hypertrophy but also cardiac fibrosis. As overexpression was restricted to cardiac myocytes (CM), we postulated that the protection involved a paracrine cross-talk to cardiac fibroblasts (CF).Methods: We developed a model of superfusion of CF in serum-free conditions with media conditioned by cultured CM with adenoviral expression of the human β3AR and treated or not with phenylephrine (PE). Cardiac extracts were analysed in wild type (WT) and heterozygote transgenic mice with cardiac myocyte-specific overexpression of human β3AR (hβ3TG) submitted to transaortic constriction (TAC) for 9 weeks.Results: Incubation of CF with medium conditioned by control CM treated with PE stimulated their proliferation, migration, myofibroblats differentiation (α-SMA expression) and pro-collagen I expression compared with medium from CM not treated with PE. This was associated with activation of the ERK pathway in CF. All these effects were abolished by heat inactivation of the media, suggesting implication of paracrinally secreted peptides. The effects of medium conditioned by untreated β3AR overexpressing CM were similar to those untreated controls. However, incubation of CF with medium of β3AR overexpressing CM treated with PE did not activate their differentiation into myofibroblats or pro-collagen I expression. Activation of the ERK pathway was also absent. To unravel the idendity of paracrine factors, the secretome of CM was submitted to shotgun proteomic analysis by LC tandem MS. Top candidates significantly downregulated in β3AR-PE conditioned medium compared with GFP-PE included CTGF, galectin-3 binding protein, plasminogen activator inhibitor 1, collagen I and III, fibronectin, thrombospondin-1. Accordingly, β3AR was associated with decreased mRNA expression of CTGF in CM in vitro. These results were confirmed in vivo after TAC stress in mice at mRNA and proteins levels (cTGF protein expression: 1.03±0.1 (WT) vs 0.51±01 (β3AR), p<0.01).Conclusion: We conclude that β3AR decreases the expression of pro-fibrotic paracrine factors such as CTGF, resulting in protection from myocardial fibrosis in response to neurohormonal stimulation. [ABSTRACT FROM AUTHOR]

Published
2014
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10. Enhanced expression of β3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase

Author

Irina Lobysheva, Dominique Langin, Jean-Luc Balligand, A.C. Pouleur, Annelies Vanderper, Konrad R. Götz, Karima Jnaoui, Christophe Beauloye, Denise Hilfiker-Kleiner, Andreas Markl, Hrag Esfahani, Emilie Dubois-Deruy, Luc Bertrand, Guido Iaccarino, Joanna Hammond, Geneviève Tavernier, Paul Herijgers, Viacheslav O. Nikolaev, Julien Hamelet, Catharina Belge, Chantal Dessy, Boris Manoury, Belge, C., Hammond, J., Dubois-Deruy, E., Manoury, B., Hamelet, J., Beauloye, C., Markl, A., Pouleur, A. -C., Bertrand, L., Esfahani, H., Jnaoui, K., Gotz, K. R., Nikolaev, V. O., Vanderper, A., Herijgers, P., Lobysheva, I., Iaccarino, G., Hilfiker-Kleiner, D., Tavernier, G., Langin, D., Dessy, C., Balligand, J. -L., Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Pole of Cardiovascular Pathology and Cliniques Universitaires Saint-Luc, Division of Cardiology and Pneumology, University of Göttingen - Georg-August-Universität Göttingen, Department of Cardiovascular Sciences, Department of Medicine and Surgery, Università degli Studi di Salerno (UNISA)-RCCS 'Multimedia', Molecular Cardiology, Medizinische Hochschule Hannover (MHH), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Georg-August-University = Georg-August-Universität Göttingen, and Università degli Studi di Salerno = University of Salerno (UNISA)-RCCS 'Multimedia'

Subjects
MESH: Signal Transduction, Male, MESH: Myocytes, Cardiac, MESH: Neurotransmitter Agents, MESH: Isoproterenol, Muscle hypertrophy, Heart Ventricle, chemistry.chemical_compound, Mice, Cyclic GMP-Dependent Protein Kinase, MESH: Cyclic GMP-Dependent Protein Kinases, Myocyte, MESH: Cyclic GMP, MESH: Animals, Myocytes, Cardiac, Cyclic GMP, Cells, Cultured, Neurotransmitter Agents, biology, MESH: Hypertrophy, Ventricular Remodeling, Angiotensin II, Receptors, adrenergic, beta, Nitric oxide synthase, Catecholamine, MESH: Nitric Oxide Synthase, MESH: Angiotensin II, Signal transduction, Cardiology and Cardiovascular Medicine, MESH: Cells, Cultured, Human, Signal Transduction, medicine.medical_specialty, MESH: Mice, Transgenic, Heart Ventricles, MESH: Ventricular Remodeling, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, In Vitro Techniques, Nitric oxide, Neurotransmitter Agent, Physiology (medical), Internal medicine, medicine, Cyclic GMP-Dependent Protein Kinases, Animals, Humans, Ventricular remodeling, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, MESH: Humans, business.industry, Animal, In Vitro Technique, Isoproterenol, Hypertrophy, medicine.disease, MESH: Male, Disease Models, Animal, Endocrinology, chemistry, Receptors, Adrenergic, beta-3, biology.protein, MESH: Heart Ventricles, MESH: Disease Models, Animal, Nitric Oxide Synthase, business, MESH: Receptors, Adrenergic, beta-3, cGMP-dependent protein kinase
Abstract

Background— β1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. β3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown. Methods and Results— Mice with cardiac myocyte-specific expression of human β3-AR (β3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). β3-TG and WT had similar morphometric and hemodynamic parameters at baseline. β3-AR colocalized with caveolin-3, endothelial nitric oxide synthase (NOS) and neuronal NOS in adult transgenic myocytes, which constitutively produced more cyclic GMP, detected with a new transgenic FRET sensor. Iso and Ang II produced hypertrophy and fibrosis in WT mice, but not in β3-TG mice, which also had less re-expression of fetal genes and transforming growth factor β1. Protection from Iso-induced hypertrophy was reversed by nonspecific NOS inhibition at low dose Iso, and by preferential neuronal NOS inhibition at high-dose Iso. Adenoviral overexpression of β3-AR in isolated cardiac myocytes also increased NO production and attenuated hypertrophy to Iso and phenylephrine. Hypertrophy was restored on NOS or protein kinase G inhibition. Mechanistically, β3-AR overexpression inhibited phenylephrine-induced nuclear factor of activated T-cell activation. Conclusions— Cardiac-specific overexpression of β3-AR does not affect cardiac morphology at baseline but inhibits the hypertrophic response to neurohormonal stimulation in vivo and in vitro, through a NOS-mediated mechanism. Activation of the cardiac β3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodeling.

Published
2014
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11. Enhanced expression of β3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase.

Author

Belge C, Hammond J, Dubois-Deruy E, Manoury B, Hamelet J, Beauloye C, Markl A, Pouleur AC, Bertrand L, Esfahani H, Jnaoui K, Götz KR, Nikolaev VO, Vanderper A, Herijgers P, Lobysheva I, Iaccarino G, Hilfiker-Kleiner D, Tavernier G, Langin D, Dessy C, and Balligand JL

Subjects
Angiotensin II adverse effects, Angiotensin II pharmacology, Animals, Cells, Cultured, Cyclic GMP physiology, Cyclic GMP-Dependent Protein Kinases physiology, Disease Models, Animal, Heart Ventricles physiopathology, Humans, Hypertrophy chemically induced, Hypertrophy pathology, Hypertrophy physiopathology, In Vitro Techniques, Isoproterenol adverse effects, Isoproterenol pharmacology, Male, Mice, Mice, Transgenic, Myocytes, Cardiac pathology, Myocytes, Cardiac physiology, Neurotransmitter Agents adverse effects, Receptors, Adrenergic, beta-3 genetics, Signal Transduction physiology, Ventricular Remodeling physiology, Heart Ventricles pathology, Myocytes, Cardiac metabolism, Neurotransmitter Agents pharmacology, Nitric Oxide Synthase physiology, Receptors, Adrenergic, beta-3 metabolism, Ventricular Remodeling drug effects
Abstract

Background: β1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. β3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown., Methods and Results: Mice with cardiac myocyte-specific expression of human β3-AR (β3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). β3-TG and WT had similar morphometric and hemodynamic parameters at baseline. β3-AR colocalized with caveolin-3, endothelial nitric oxide synthase (NOS) and neuronal NOS in adult transgenic myocytes, which constitutively produced more cyclic GMP, detected with a new transgenic FRET sensor. Iso and Ang II produced hypertrophy and fibrosis in WT mice, but not in β3-TG mice, which also had less re-expression of fetal genes and transforming growth factor β1. Protection from Iso-induced hypertrophy was reversed by nonspecific NOS inhibition at low dose Iso, and by preferential neuronal NOS inhibition at high-dose Iso. Adenoviral overexpression of β3-AR in isolated cardiac myocytes also increased NO production and attenuated hypertrophy to Iso and phenylephrine. Hypertrophy was restored on NOS or protein kinase G inhibition. Mechanistically, β3-AR overexpression inhibited phenylephrine-induced nuclear factor of activated T-cell activation., Conclusions: Cardiac-specific overexpression of β3-AR does not affect cardiac morphology at baseline but inhibits the hypertrophic response to neurohormonal stimulation in vivo and in vitro, through a NOS-mediated mechanism. Activation of the cardiac β3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodeling.

Published
2014
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12. HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic dysfunction through AMP-activated protein kinase activation in a mouse model of metabolic syndrome.

Author

Hermida N, Markl A, Hamelet J, Van Assche T, Vanderper A, Herijgers P, van Bilsen M, Hilfiker-Kleiner D, Noppe G, Beauloye C, Horman S, and Balligand JL

Subjects
AMP-Activated Protein Kinases genetics, Actins metabolism, Animals, Cells, Cultured, Collagen Type I metabolism, Diastole, Disease Models, Animal, Enzyme Activation, Fibroblasts drug effects, Fibroblasts enzymology, Fibroblasts pathology, Fibrosis, Heart Diseases enzymology, Heart Diseases genetics, Heart Diseases pathology, Heart Diseases physiopathology, Leptin deficiency, Leptin genetics, Metabolic Syndrome enzymology, Metabolic Syndrome genetics, Metabolic Syndrome pathology, Metabolic Syndrome physiopathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardium pathology, Procollagen metabolism, Rats, Receptors, LDL deficiency, Receptors, LDL genetics, Recovery of Function, Rosuvastatin Calcium, Signal Transduction drug effects, Time Factors, Transfection, Transforming Growth Factor beta1 metabolism, Ventricular Remodeling drug effects, AMP-Activated Protein Kinases metabolism, Fluorobenzenes pharmacology, Heart Diseases drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Metabolic Syndrome drug therapy, Myocardium enzymology, Pyrimidines pharmacology, Sulfonamides pharmacology, Ventricular Function, Left drug effects
Abstract

Aims: The metabolic syndrome (MS) leads to myocardial fibrosis (MF) and diastolic dysfunction. Statins have proven beneficial effects in MS, but their impact on cardiac remodelling is uncertain. We examined the effects and mechanisms of chronic statin treatment on cardiac remodelling, e.g. fibrosis and diastolic properties., Methods and Results: We used a mouse model deficient in leptin and the LDL-receptor (DKO) that reproduces this MS phenotype. DKO mice (12 weeks) were treated with rosuvastatin (R) for 6 months vs. placebo. Morphometric and echocardiographic measurements showed that R reduced cardiac mass and increased left-ventricular end-diastolic diameter despite unchanged cardiomyocyte dimensions. Similarly, R had no effect on the hypertrophic response to neurohormones in isolated cardiomyocytes. Conversely, R reversed the age-dependent development of MF as well as mRNA expression of TGF-β1 and several pro-fibrotic markers (procollagen type I, its carboxy-terminal proteinase, Lysyl oxidase). R similarly inhibited the pro-fibrotic effects of TGF-β1 on procollagen type I, alpha Smooth Muscle Actin expression and migratory properties of cardiac fibroblasts in vitro. In parallel, R increased the activation of AMP-activated protein kinase (AMPK), a known inhibitor of fibrosis, in vivo and in vitro, and the anti-fibrotic effects of R were abrogated in fibroblasts transfected with AMPKα1/α2 siRNA. The reversal of MF by R in DKO mice was accompanied with improved diastolic properties assessed by P-V loop analysis (slope of EDPVR, dP/dt min and cardiac output)., Conclusion: In this model of MS, statin treatment reverses myocardial remodelling and improves ventricular relaxation through AMPK-mediated anti-fibrotic effects.

Published
2013
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13. Effects of red wine polyphenolic compounds on paraoxonase-1 and lectin-like oxidized low-density lipoprotein receptor-1 in hyperhomocysteinemic mice.

Author

Noll C, Hamelet J, Matulewicz E, Paul JL, Delabar JM, and Janel N

Subjects
Animals, Antioxidants pharmacology, Aorta enzymology, Aryldialkylphosphatase blood, Aryldialkylphosphatase genetics, Biomarkers, Caffeic Acids pharmacology, Cystathionine beta-Synthase deficiency, Cystathionine beta-Synthase drug effects, Disease Models, Animal, Female, Flavonoids administration & dosage, Heterozygote, Homocysteine blood, Hyperhomocysteinemia prevention & control, Lipid Peroxidation drug effects, Liver drug effects, Liver enzymology, Male, Methionine administration & dosage, Methionine metabolism, Mice, Mice, Inbred C57BL, Phenols administration & dosage, Polyphenols, Receptors, Oxidized LDL blood, Receptors, Oxidized LDL genetics, Aryldialkylphosphatase metabolism, Flavonoids pharmacology, Gene Expression Regulation, Enzymologic drug effects, Hyperhomocysteinemia metabolism, Phenols pharmacology, Receptors, Oxidized LDL metabolism, Wine
Abstract

Hyperhomocysteinemia, or abnormally high plasma homocysteine (Hcy) concentration, has often been associated with vascular thrombosis and the development of premature atherosclerosis. Many studies have shown that moderate wine consumption has potential beneficial effects related to the prevention of atherosclerosis, in part attributed to the biological properties of polyphenolic components, mainly flavonoids. The aim of the present study is to determine the effects of a red wine polyphenolic extract (PE) administration on hyperhomocysteinemia due to cystathionine beta-synthase (CBS) deficiency and on the associated biochemical markers of hepatic and endothelial dysfunctions in mice. Red wine PE was added for 4 weeks to the drinking water of heterozygous CBS-deficient mice fed a high-methionine diet, a murine model of hyperhomocysteinemia. Red wine PE supplementation at low dose significantly reduced plasma Hcy levels and restored the hepatic and plasma-decreased paraoxonase-1 activity induced by chronic hyperhomocysteinemia. Moreover, aortic expression of proinflammatory cytokines and adhesion molecules and levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 were reduced in hyperhomocysteinemic mice fed the red wine PE supplementation. These findings suggest that red wine PE administration in low quantities has beneficial effects on biochemical markers of endothelial dysfunction due to hyperhomocysteinemia.

Published
2009
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14. Calpain activation is required for homocysteine-mediated hepatic degradation of inhibitor I kappa B alpha.

Author

Hamelet J, Couty JP, Crain AM, Noll C, Postic C, Paul JL, Delabar JM, Viguier M, and Janel N

Subjects
Animals, Apoptosis genetics, Apoptosis Regulatory Proteins genetics, Cystathionine beta-Synthase deficiency, Cystathionine beta-Synthase genetics, Fatty Liver pathology, Gene Expression, Hepatocytes enzymology, Hepatocytes pathology, Homocysteine metabolism, Hyperhomocysteinemia enzymology, Hyperhomocysteinemia genetics, Kupffer Cells metabolism, Liver enzymology, Liver pathology, Mice, Mice, Mutant Strains, NF-KappaB Inhibitor alpha, Phosphorylation, Calpain biosynthesis, Fatty Liver enzymology, Fatty Liver etiology, Hyperhomocysteinemia complications, I-kappa B Proteins metabolism
Abstract

Hepatic steatosis is a clinical feature observed in severe hyperhomocysteinemic patients. In mice, cystathionine beta synthase (CBS) deficiency, the most common cause of severe hyperhomocysteinemia, is also associated with steatosis, fibrosis and inflammation. Proinflammatory cytokines usually induce apoptosis. However, hyperhomocysteinemia does not increase apoptosis in liver of CBS-deficient mice compared to wild type mice. The aim of the study was to analyze the activation state of the NF-kappaB pathway in liver of CBS-deficient mice and to investigate its possible involvement in anti-apoptotic signals. We analyzed the level of I kappaB alpha in liver of CBS-deficient mice. A co-culture of primary hepatocytes and Kupffer cells was also used in order to investigate how I kappaB alpha degradation occurs in response to homocysteine. We found lower I kappaB alpha level not only in liver of CBS-deficient mice but also in hepatocyte/Kupffer cell co-culture. The homocysteine-mediated I kappaB alpha enhanced proteolysis occurred via calcium-dependent calpains, which was supported by an increased level of calpain activity and a reduced expression of calpastatin in liver of CBS-deficient mice. Intraperitoneal administration of the inhibitor PDTC normalized the expression of two genes induced by NF-kappaB activation, heme oxygenase-1 and cellular inhibitor of apoptosis 2. Moreover, PDTC administration induced an increase of caspase-3 activity in liver of CBS-deficient mice. Our results suggest that hyperhomocysteinemia induces calpain-mediated I kappaB alpha degradation which is responsible for anti-apoptotic signals in liver.

Published
2009
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15. Effect of hyperhomocysteinemia on the protein kinase DYRK1A in liver of mice.

Author

Hamelet J, Noll C, Ripoll C, Paul JL, Janel N, and Delabar JM

Subjects
Animals, Calpain metabolism, Coculture Techniques, Cystathionine beta-Synthase genetics, Disease Models, Animal, Enzyme Activation, Glycoproteins pharmacology, Hepatocytes enzymology, Hyperhomocysteinemia genetics, Kupffer Cells enzymology, Liver drug effects, Mice, Mice, Knockout, Dyrk Kinases, Hyperhomocysteinemia enzymology, Liver enzymology, Protein Serine-Threonine Kinases metabolism, Protein-Tyrosine Kinases metabolism
Abstract

Hyperhomocysteinemia due to cystathionine beta synthase (CBS)-deficiency confers diverse clinical manifestations, notably liver diseases. Even if hyperhomocysteinemia in liver of CBS-deficient mice, a murine model of hyperhomocysteinemia, promotes mitochondrial oxidative stress and pro-apoptotic signals, protective signals may counteract these pro-apoptotic signals, leading to chronic inflammation. As DYRK1A, a serine/threonine kinase, has been described as a candidate antiapoptotic factor, we have analyzed the expression of DYRK1A in liver of CBS-deficient mice. We found that DYRK1A protein level was reduced in liver of CBS-deficient mice, which was not observed at the gene expression level. Moreover, the use of primary hepatocytes/Kupffer cells co-culture showed that degradation of DYRK1A induced by hyperhomocysteinemia requires calpain activation. Our results demonstrate a deleterious effect of hyperhomocysteinemia on DYRK1A protein expression, and emphasize the role of hyperhomocysteinemia on calpain activation.

Published
2009
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16. Resveratrol supplementation worsen the dysregulation of genes involved in hepatic lipid homeostasis observed in hyperhomocysteinemic mice.

Author

Noll C, Hamelet J, Ducros V, Belin N, Paul JL, Delabar JM, and Janel N

Subjects
Animals, Apolipoprotein A-I genetics, Apolipoprotein A-I metabolism, Cystathionine beta-Synthase metabolism, Dietary Supplements, Genotype, Hyperhomocysteinemia genetics, Hyperhomocysteinemia metabolism, Mice, Phosphatidylcholine-Sterol O-Acyltransferase metabolism, Resveratrol, S-Adenosylhomocysteine metabolism, S-Adenosylmethionine metabolism, Scavenger Receptors, Class B genetics, Scavenger Receptors, Class B metabolism, Gene Expression Regulation drug effects, Lipid Metabolism drug effects, Lipid Metabolism genetics, Liver drug effects, Liver metabolism, Stilbenes pharmacology
Abstract

Hyperhomocysteinemia is characterized by an increase of plasma homocysteine, a thiol-containing amino acid produced during methionine metabolism. Hyperhomocysteinemia has often been associated with coronary artery disease, vascular thrombosis and the development of premature atherosclerosis. We have recently demonstrated that the supplementation of catechin, a polyphenol found in the red wine, significantly reduced plasma homocysteine level in cystathionine beta synthase (CBS) deficient mice, a murine model of hyperhomocysteinemia. In the present study, we have investigated the influence of another well-studied polyphenol found in red wine, resveratrol, on hyperhomocysteinemia. After two months on high methionine diet, heterozygous Cbs deficient mice were administrated the resveratrol in drinking water (0.001%) for one month. High methionine diet significantly increased serum homocysteine levels, and decreased the serum activity of HDL-associated enzyme paraoxonase-1. Chronic administration of resveratrol significantly increased plasma homocysteine level, which was associated with a decreased serum paraoxonase-1 activity, in hyperhomocysteinemic mice. Then we looked at gene expression of several proteins involved in HDL stability and found a down-regulation of lecithin:cholesterol acyltransferase. In conclusion, we found a deleterious effect of resveratrol onto homocysteine and HDL metabolism in a murine model of hyperhomocysteinemia.

Published
2009
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17. Cystathionine beta synthase deficiency induces catalase-mediated hydrogen peroxide detoxification in mice liver.

Author

Hamelet J, Seltzer V, Petit E, Noll C, Andreau K, Delabar JM, and Janel N

Subjects
Animals, Base Sequence, Catalase genetics, Cystathionine beta-Synthase genetics, DNA Primers genetics, Disease Models, Animal, Female, Heme Oxygenase-1 genetics, Heme Oxygenase-1 metabolism, Heterozygote, Homocystinuria genetics, Homocystinuria metabolism, Humans, Hyperhomocysteinemia genetics, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, NADPH Oxidases metabolism, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism, Superoxide Dismutase genetics, Superoxide Dismutase metabolism, Superoxide Dismutase-1, Catalase metabolism, Cystathionine beta-Synthase deficiency, Hydrogen Peroxide metabolism, Hyperhomocysteinemia metabolism, Liver metabolism
Abstract

Cystathionine beta synthase deficiency induces hyperhomocysteinemia which is considered as a risk factor for vascular diseases. Studies underlined the importance of altered cellular redox reactions in hyperhomocysteinemia-induced vascular pathologies. Nevertheless, hyperhomocysteinemia also induces hepatic dysfunction which may accelerate the development of vascular pathologies by modifying cholesterol homeostasis. The aim of the present study was to analyze the modifications of redox state in the liver of heterozygous cystathionine beta synthase-deficient mice, a murine model of hyperhomocysteinemia. In this purpose, we quantified levels of reactive oxygen and nitrogen species and we assayed activities of main antioxidant enzymes. We found that cystathionine beta synthase deficiency induced NADPH oxidase activation. However, there was no accumulation of reactive oxygen (superoxide anion, hydrogen peroxide) and nitrogen (nitrite, peroxynitrite) species. On the contrary, hepatic hydrogen peroxide level was decreased independently of an activation of glutathione-dependent mechanisms. In fact, cystathionine beta synthase deficiency had no effect on glutathione peroxidase, glutathione reductase and glutathione S-transferase activities. However, we found a 50% increase in hepatic catalase activity without any variation of expression. These findings demonstrate that cystathionine beta synthase deficiency initiates redox disequilibrium in the liver. However, the activation of catalase attenuates oxidative impairments.

Published
2008
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18. Mice lacking cystathionine beta synthase have lung fibrosis and air space enlargement.

Author

Hamelet J, Maurin N, Fulchiron R, Delabar JM, and Janel N

Subjects
Animals, Cell Differentiation, Disease Models, Animal, Fibroblasts pathology, Homocysteine blood, Hyperhomocysteinemia complications, Mice, Mice, Knockout, Polymerase Chain Reaction, Pulmonary Disease, Chronic Obstructive etiology, Pulmonary Fibrosis enzymology, Cystathionine beta-Synthase deficiency, Pulmonary Fibrosis pathology
Abstract

Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations, notably pulmonary thrombotic disease. However, the association between hyperhomocysteinemia and chronic obstructive pulmonary disease is not well understood. To investigate the role of hyperhomocysteinemia in lung injury and pulmonary fibrosis, we analyzed the lung of CBS-deficient mice, a murine model of severe hyperhomocysteinemia. The degree of lung injury was assessed by histologic examination. Analysis of profibrogenic factors was performed by real-time quantitative reverse transcription-polymerase chain reaction. CBS-deficient mice develop fibrosis and air space enlargement in the lung, concomitant with an enhanced expression of heme oxygenase-1, pro(alpha)1 collagen type I, transforming growth factor-beta1 and alpha-smooth muscle actin. However, lung fibrosis was found in the absence of increased inflammatory cell infiltrates as determined by histology, without changes in gene expression of proinflammatory cytokines TNFalpha and interleukin 6. The increased expression of alpha-smooth muscle actin and transforming growth factor-beta1 emphasizes the role of myofibroblasts differentiation in case of lung fibrosis due to CBS deficiency in mice.

Published
2007
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19. Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway.

Author

Alberto JM, Hamelet J, Noll C, Blaise S, Bronowicki JP, Guéant JL, Delabar JM, and Janel N

Subjects
Animals, Cystathionine beta-Synthase genetics, Disease Models, Animal, Methylation, Mice, MicroRNAs genetics, Homocysteine metabolism, Homocystinuria genetics, Homocystinuria metabolism
Abstract

Cystathionine beta synthase (CBS) deficiency is a metabolic disorder that is biochemically characterized by severe hyperhomocysteinemia. In order to show the effects of CBS deficiency onto the activity of the enzymes involved in the remethylation pathway, we used the well characterized genetic model of severe hyperhomocysteinemia in mice. We showed that CBS deficiency in mice reduced hepatic methionine synthase and betaine-homocysteine methyltransferase activities, whereas 5,10-methylene tetrahydrofolate reductase activity was increased.

Published
2007
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20. Effects of catechin on homocysteine metabolism in hyperhomocysteinemic mice.

Author

Hamelet J, Demuth K, Dairou J, Ledru A, Paul JL, Dupret JM, Delabar JM, Rodrigues-Lima F, and Janel N

Subjects
Administration, Oral, Animal Feed, Animals, Cystathionine beta-Synthase genetics, DNA Primers, Hyperhomocysteinemia genetics, Liver metabolism, Methionine administration & dosage, Methionine pharmacology, Mice, RNA genetics, RNA isolation & purification, Reverse Transcriptase Polymerase Chain Reaction, Superoxide Dismutase genetics, Superoxide Dismutase-1, Catechin pharmacology, Homocysteine metabolism, Hyperhomocysteinemia metabolism
Abstract

We have recently focused on the interaction between hyperhomocysteinemia, defined by high plasma homocysteine levels, and paraoxonase-1 expression and found a reduced activity of paraoxonase-1 associated with a reduced gene expression in the liver of cystathionine beta synthase (CBS) deficient mice, a murine model of hyperhomocysteinemia. As it has been demonstrated that polyphenolic compounds could modulate the expression level of the paraoxonase-1 gene in vitro, we have investigated the possible effect of flavonoid supplementation on the impaired paraoxonase-1 gene expression and activity induced by hyperhomocysteinemia and have evaluated the link with homocysteine metabolism. High-methionine diet significantly increased serum homocysteine levels, decreased hepatic CBS activity, and down-regulated paraoxonase-1 mRNA and its activity. However, chronic administration of catechin but not quercetin significantly reduced plasma homocysteine levels, attenuated the reduction of the hepatic CBS activity, and restored the decreased paraoxonase-1 gene expression and activity induced by chronic hyperhomocysteinemia. These data suggest that catechin could act on the homocysteine levels by increasing the rate of catabolism of homocysteine.

Published
2007
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21. Hyperhomocysteinemia due to cystathionine beta synthase deficiency induces dysregulation of genes involved in hepatic lipid homeostasis in mice.

Author

Hamelet J, Demuth K, Paul JL, Delabar JM, and Janel N

Subjects
Animals, Base Sequence, Cholesterol metabolism, DNA Primers genetics, Disease Models, Animal, Endoplasmic Reticulum metabolism, Homocysteine blood, Homocystinuria complications, Homocystinuria genetics, Homocystinuria metabolism, Hyperhomocysteinemia enzymology, Hyperhomocysteinemia genetics, Lipid Metabolism, Liver metabolism, Male, Mice, Mice, Knockout, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Cytoplasmic and Nuclear genetics, Cystathionine beta-Synthase deficiency, Cystathionine beta-Synthase genetics, Hyperhomocysteinemia etiology
Abstract

Background/aims: Cystathionine beta synthase (CBS) deficiency leads to severe hyperhomocysteinemia, which confers diverse clinical manifestations, notably fatty liver. Recently, abnormal lipid metabolism has been demonstrated in CBS-deficient mice, a murine model of severe hyperhomocysteinemia. To gain further insights into effects of CBS deficiency on hepatic cholesterol metabolism, the expression of hepatic genes involved in biosynthesis, uptake and efflux was determined in CBS-deficient mice., Methods: Gene expression analysis was performed on liver of CBS-deficient mice using quantitative real-time PCR., Results: We found that CBS-deficiency in liver mice significantly increases expression of genes induced by endoplasmic reticulum stress and genes that regulate the expression of enzymes required for cholesterol and fatty acid biosynthesis and uptake, notably the scavenger receptor class B type I (SR-BI), concomitant with overexpression of SR-BI at the protein level. Moreover, we also found increased mRNA levels of ABCG5, ABCG8, ABCG1 and ABCA1, which play important roles in reverse cholesterol transport, associated with an upregulation of liver X receptors and a downregulation of the peroxisome proliferators-activated receptor alpha., Conclusions: We found that several ATP-binding cassette transporters and nuclear hormone receptors involved in liver lipid homeostasis are differentially expressed in liver of CBS-deficient mice.

Published
2007
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22. Paraoxonase-1 expression is up-regulated in Down syndrome fetal liver.

Author

Janel N, Christophe O, Aït Yahya-Graison E, Hamelet J, Paly E, Prieur M, Delezoïde AL, and Delabar JM

Subjects
Aryldialkylphosphatase genetics, Fetus anatomy & histology, Humans, Liver metabolism, Up-Regulation, Aryldialkylphosphatase metabolism, Down Syndrome metabolism, Gene Expression physiology
Abstract

Patients with Down syndrome appear to be protected from the development of atherosclerosis. On the contrary, hyperhomocysteinemia is associated with an increased risk for atherosclerosis. As hyperhomocysteinemia due to cystathionine beta synthase deficiency is associated with a decreased expression of paraoxonase-1, a major anti-atherosclerotic component secreted by the liver, we aimed to analyze the expression of paraoxonase-1 and cystathionine beta synthase in Down syndrome fetal liver by quantitative real-time reverse transcriptase-polymerase chain reaction. Paraoxonase-1 was up-regulated in Down syndrome fetal liver, while cystathionine beta synthase gene expression in Down syndrome fetuses was similar to the gene level in control fetuses. Moreover, there was no evidence for an association between paraoxonase-1 genotypes influencing paraoxonase-1 gene expression and Down syndrome. Since most serum paraoxonase-1 is synthesized in the liver, an increase of hepatic paraoxonase-1 expression might be one of the factors which could explain the low incidence of atherosclerotic vascular disease in Down syndrome.

Published
2006
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