Search

Your search keyword '"Somoza B"' showing total 137 results
Start Over Author "Somoza B"
137 results on '"Somoza B"'

17. PP.28.05

Author

Gil-Ortega, M., primary, García-Prieto, C.F., additional, Hurtado, G. Ruiz, additional, Steireif, C., additional, González, M.C., additional, Schulz, A., additional, Kreutz, R., additional, Fernández-Alfonso, M.S., additional, Arribas, S.M., additional, and Somoza, B., additional

Published
2015
Full Text
View/download PDF

18. 8D.08

Author

Pulido-Olmo, H., primary, Gracia-Prieto, C.F., additional, Somoza, B., additional, Aránguez, I., additional, Alvarez-Llamas, G., additional, Vivanco, F., additional, Barderas, M.G., additional, Kreutz, R., additional, Segura, J., additional, Fernández-Alfonso, M.S., additional, Ruilope, L.M., additional, and Ruiz-Hurtado, G., additional

Published
2015
Full Text
View/download PDF

20. 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
Full Text
View/download PDF

35. P490 Perinatal programming of cardiometabolic diseases: early alterations in adipose tissue and organ development in animal models.

Author

Lopez De Pablo, AL, Rodriguez-Rodriguez, P, Gutierrez, PY, Gonzalez, MC, Munnoz, D, Somoza, B, and Arribas, SM

Subjects
HEART metabolism, HEART diseases, ADIPOSE tissues, MORPHOGENESIS, ANIMAL models in research, GESTATIONAL age
Abstract

Purpose: Fetal stress and postnatal overfeeding are associated with programming of cardiometabolic diseases, but their relative role is not clearly established. By using specific animal models we aimed to address this issue comparing the perinatal alterations induced in several organs key for cardiometabolic control.Methods: Fetal stress was induced by maternal undernutrition (MUN) during pregnancy. MUN rats were fed ad libitum with standard chow from gestational day 1 to 10; with 50% of their daily intake from day 11 to the end of pregnancy and returned back to ad libitum during lactation (12 pups/litter). Postnatal overfeeding (POF) was induced in the offspring from ad libitum fed dams by reducing litter size during lactation (4 pups/litter). Control animals were offspring from dams ad libitum fed both during pregnancy and lactation (12 pups/litter). Tibial length and body, heart, kidney, liver and fat adipose tissue weights, as well as adipocites size, were assessed in the offspring at weaning (21 days). A group of MUN offspring was followed to measure body weight along perinatal development.Results: MUN offspring showed reduced tibial length and body weight from birth with progressive catch-up growth until month two, when body weight reached similar values to control rats. By weaning MUN offspring rats exhibited: 1) hyperglycemia; 2) heart and liver hypertrophy, 3) reduced kidney weight and 4) increased subcutaneous and periorganic fat deposits and adipocite size. POF offspring also exhibited increased glycemia together with liver, fat and body weight and adipocite size, but heart and kidney weights were not altered. There were no sex-related differences in either MUN or POF models in any of the parameters studied.Conclusions: We conclude that accelerated growth during postnatal life, rather than fetal stress, seems to be critical for metabolic control organs alterations. On the other hand, fetal stress induces changes in heart and kidney at an early age which might have a direct role on later cardiovascular disease development. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

37. Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity.

Author

Alvarez-Gallego F, González-Blázquez R, Gil-Ortega M, Somoza B, Calderón-Dominguez M, Moratinos J, Garcia-Garcia V, Fernández P, González-Moreno D, Viana M, and Alcalá M

Subjects
Animals, Male, Mice, Adipocytes, Brown, Mice, Inbred C57BL, Obesity drug therapy, Obesity genetics, Obesity metabolism, Uncoupling Protein 1 genetics, Uncoupling Protein 1 metabolism, Adipose Tissue, Brown, Receptor, Angiotensin, Type 2 genetics, Receptor, Angiotensin, Type 2 agonists, Receptor, Angiotensin, Type 2 metabolism
Abstract

The angiotensin II type 2 receptor (AT2R) exerts vasorelaxant, anti-inflammatory, and antioxidant properties. In obesity, its activation counterbalances the adverse cardiovascular effects of angiotensin II mediated by the AT1R. Preliminary results indicate that it also promotes brown adipocyte differentiation in vitro. Our hypothesis is that AT2R activation could increase BAT mass and activity in obesity. Five-week-old male C57BL/6J mice were fed a standard or a high-fat (HF) diet for 6 weeks. Half of the animals were treated with compound 21 (C21), a selective AT2R agonist, (1 mg/kg/day) in the drinking water. Electron transport chain (ETC), oxidative phosphorylation, and UCP1 proteins were measured in the interscapular BAT (iBAT) and thoracic perivascular adipose tissue (tPVAT) as well as inflammatory and oxidative parameters. Differentiation and oxygen consumption rate (OCR) in the presence of C21 was tested in brown preadipocytes. In vitro, C21-differentiated brown adipocytes showed an AT2R-dependent increase of differentiation markers (Ucp1, Cidea, Pparg) and increased basal and H + leak-linked OCR. In vivo, HF-C21 mice showed increased iBAT mass compared to HF animals. Both their iBAT and tPVAT showed higher protein levels of the ETC protein complexes and UCP1, together with a reduction of inflammatory and oxidative markers. The activation of the AT2R increases BAT mass, mitochondrial activity, and reduces markers of tissue inflammation and oxidative stress in obesity. Therefore, insulin reduction and better vascular responses are achieved. Thus, the activation of the protective arm of the renin-angiotensin system arises as a promising tool in the treatment of obesity., (© 2023 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Published
2023
Full Text
View/download PDF

38. Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway.

Author

González-Blázquez R, Gil-Ortega M, Alcalá M, González-Moreno D, Viana M, Chowen JA, Sanz-Gómez M, Fernández-Alfonso MS, and Somoza B

Subjects
Mice, Male, Animals, Up-Regulation, Obesity metabolism, Signal Transduction, Diet, High-Fat adverse effects, Mice, Inbred C57BL, AMP-Activated Protein Kinases metabolism, Vascular Diseases
Abstract

Aim: In addition to functioning as an energy sensor switch, AMPK plays a key role in the maintenance of cardiovascular homeostasis. However, obesity disrupts AMPK signaling, contributing to endothelial dysfunction and cardiovascular disease. This study aimed to elucidate if a short-term dietary intervention consisting in replacing the high-fat diet with a standard diet for 2 weeks could reverse obesity-induced endothelial dysfunction via AMPK-CREB activation., Methods: For this, 5-week-old male C57BL6J mice were fed a standard (Chow) or a high-fat (HF) diet for 8 weeks. The HF diet was replaced by the chow diet for the last 2 weeks in half of HF mice, generating 3 groups: Chow, HF and HF-Chow. Vascular reactivity and western-blot assays were performed in the thoracic aorta., Results: Returning to a chow diet significantly reduced body weight and glucose intolerance. Relaxant responses to acetylcholine and the AMPK activator (AICAR) were significantly impaired in HF mice but improved in HF-Chow mice. The protein levels of AMPKα, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice., Conclusion: Improving dietary intake by replacing a HF diet with a standard diet improves AMPK-mediated responses due to the upregulation of the AMPK/CREB/HO-1 signaling pathway., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Published
2023
Full Text
View/download PDF

39. Effects of saturated versus unsaturated fatty acids on metabolism, gliosis, and hypothalamic leptin sensitivity in male mice.

Author

Fernández-Felipe J, Valencia-Avezuela M, Merino B, Somoza B, Cano V, Sanz-Martos AB, Frago LM, Fernández-Alfonso MS, Ruiz-Gayo M, and Chowen JA

Subjects
Mice, Male, Animals, Dietary Fats, Fatty Acids, Unsaturated pharmacology, Obesity metabolism, Hypothalamus metabolism, Fatty Acids metabolism, RNA, Messenger metabolism, Leptin, Gliosis metabolism
Abstract

Background: Development of obesity and its comorbidities is not only the result of excess energy intake, but also of dietary composition. Understanding how hypothalamic metabolic circuits interpret nutritional signals is fundamental to advance towards effective dietary interventions., Objective: We aimed to determine the metabolic response to diets enriched in specific fatty acids., Methods: Male mice received a diet enriched in unsaturated fatty acids (UOLF) or saturated fatty acids (SOLF) for 8 weeks., Results: UOLF and SOLF mice gained more weight and adiposity, but with no difference between these two groups. Circulating leptin levels increased on both fatty acid-enriched diet, but were higher in UOLF mice, as were leptin mRNA levels in visceral adipose tissue. In contrast, serum non-esterified fatty acid levels only rose in SOLF mice. Hypothalamic mRNA levels of NPY decreased and of POMC increased in both UOLF and SOLF mice, but only SOLF mice showed signs of hypothalamic astrogliosis and affectation of central fatty acid metabolism. Exogenous leptin activated STAT3 in the hypothalamus of all groups, but the activation of AKT and mTOR and the decrease in AMPK activation in observed in controls and UOLF mice was not found in SOLF mice., Conclusions: Diets rich in fatty acids increase body weight and adiposity even if energy intake is not increased, while increased intake of saturated and unsaturated fatty acids differentially modify metabolic parameters that could underlie more long-term comorbidities. Thus, more understanding of how specific nutrients affect metabolism, weight gain, and obesity associated complications is necessary.

Published
2023
Full Text
View/download PDF

40. AT2R stimulation with C21 prevents arterial stiffening and endothelial dysfunction in the abdominal aorta from mice fed a high-fat diet.

Author

González-Blázquez R, Alcalá M, Cárdenas-Rebollo JM, Viana M, Steckelings UM, Boisvert WA, Unger T, Fernández-Alfonso MS, Somoza B, and Gil-Ortega M

Subjects
Animals, Anti-Inflammatory Agents pharmacology, Collagen metabolism, Male, Matrix Metalloproteinase 2 blood, Matrix Metalloproteinase 9 blood, Mice, Inbred C57BL, Obesity metabolism, Receptor, Angiotensin, Type 2 agonists, Transforming Growth Factor beta1 blood, Mice, Aorta, Abdominal drug effects, Diet, High-Fat adverse effects, Imidazoles pharmacology, Sulfonamides pharmacology, Thiophenes pharmacology, Vascular Stiffness drug effects
Abstract

The aim of the present study was to evaluate the effect of Compound 21 (C21), a selective AT2R agonist, on the prevention of endothelial dysfunction, extracellular matrix (ECM) remodeling and arterial stiffness associated with diet-induced obesity (DIO). Five-week-old male C57BL/6J mice were fed a standard (Chow) or high-fat diet (HF) for 6 weeks. Half of the animals of each group were simultaneously treated with C21 (1 mg/kg/day, in the drinking water), generating four groups: Chow C, Chow C21, HF C, and HF C21. Vascular function and mechanical properties were determined in the abdominal aorta. To evaluate ECM remodeling, collagen deposition and TGF-β1 concentrations were determined in the abdominal aorta and the activity of metalloproteinases (MMP) 2 and 9 was analyzed in the plasma. Abdominal aortas from HF C mice showed endothelial dysfunction as well as enhanced contractile but reduced relaxant responses to Ang II. This effect was abrogated with C21 treatment by preserving NO availability. A left-shift in the tension-stretch relationship, paralleled by an augmented β-index (marker of intrinsic arterial stiffness), and enhanced collagen deposition and MMP-2/-9 activities were also detected in HF mice. However, when treated with C21, HF mice exhibited lower TGF-β1 levels in abdominal aortas together with reduced MMP activities and collagen deposition compared with HF C mice. In conclusion, these data demonstrate that AT2R stimulation by C21 in obesity preserves NO availability and prevents unhealthy vascular remodeling, thus protecting the abdominal aorta in HF mice against the development of endothelial dysfunction, ECM remodeling and arterial stiffness., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Published
2021
Full Text
View/download PDF

41. C21 preserves endothelial function in the thoracic aorta from DIO mice: role for AT2, Mas and B2 receptors.

Author

González-Blázquez R, Alcalá M, Fernández-Alfonso MS, Steckelings UM, Lorenzo MP, Viana M, Boisvert WA, Unger T, Gil-Ortega M, and Somoza B

Subjects
Animals, Aorta, Thoracic drug effects, Cyclic AMP-Dependent Protein Kinases metabolism, Diet, High-Fat, Drug Evaluation, Preclinical, Human Umbilical Vein Endothelial Cells, Humans, Imidazoles pharmacology, Male, Mice, Inbred C57BL, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Obesity complications, Obesity metabolism, Proto-Oncogene Mas, Proto-Oncogene Proteins c-akt metabolism, Receptor Cross-Talk, Receptor, Angiotensin, Type 2 metabolism, Renin-Angiotensin System drug effects, Signal Transduction drug effects, Sulfonamides pharmacology, Thiophenes pharmacology, Vascular Diseases etiology, Vascular Diseases metabolism, Mice, Endothelium, Vascular drug effects, Imidazoles therapeutic use, Proto-Oncogene Proteins metabolism, Receptor, Angiotensin, Type 2 agonists, Receptor, Bradykinin B2 metabolism, Receptors, G-Protein-Coupled metabolism, Sulfonamides therapeutic use, Thiophenes therapeutic use, Vascular Diseases prevention & control
Abstract

Compound 21 (C21), a selective agonist of angiotensin II type 2 receptor (AT2R), induces vasodilation through NO release. Since AT2R seems to be overexpressed in obesity, we hypothesize that C21 prevents the development of obesity-related vascular alterations. The main goal of the present study was to assess the effect of C21 on thoracic aorta endothelial function in a model of diet-induced obesity (DIO) and to elucidate the potential cross-talk among AT2R, Mas receptor (MasR) and/or bradykinin type 2 receptor (B2R) in this response. Five-week-old male C57BL6J mice were fed a standard (CHOW) or a high-fat diet (HF) for 6 weeks and treated daily with C21 (1 mg/kg p.o) or vehicle, generating four groups: CHOW-C, CHOW-C21, HF-C, HF-C21. Vascular reactivity experiments were performed in thoracic aorta rings. Human endothelial cells (HECs; EA.hy926) were used to elucidate the signaling pathways, both at receptor and intracellular levels. Arteries from HF mice exhibited increased contractions to Ang II than CHOW mice, effect that was prevented by C21. PD123177, A779 and HOE-140 (AT2R, Mas and B2R antagonists) significantly enhanced Ang II-induced contractions in CHOW but not in HF-C rings, suggesting a lack of functionality of those receptors in obesity. C21 prevented those alterations and favored the formation of AT2R/MasR and MasR/B2R heterodimers. HF mice also exhibited impaired relaxations to acetylcholine (ACh) due to a reduced NO availability. C21 preserved NO release through PKA/p-eNOS and AKT/p-eNOS signaling pathways. In conclusion, C21 favors the interaction among AT2R, MasR and B2R and prevents the development of obesity-induced endothelial dysfunction by stimulating NO release through PKA/p-eNOS and AKT/p-eNOS signaling pathways., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Published
2021
Full Text
View/download PDF

42. Differential Deleterious Impact of Highly Saturated Versus Monounsaturated Fat Intake on Vascular Function, Structure, and Mechanics in Mice.

Author

Vega-Martín E, Gil-Ortega M, González-Blázquez R, Benedito S, Fernández-Felipe J, Ruiz-Gayo M, Del Olmo N, Chowen JA, Frago LM, Somoza B, and Fernández-Alfonso MS

Subjects
Animals, Aorta, Thoracic drug effects, Arteries physiology, Body Weight, Collagen metabolism, Diet, High-Fat, Dietary Fats, Unsaturated pharmacology, Elastin, Fatty Acids pharmacology, Fuchs' Endothelial Dystrophy, Glucose metabolism, Male, Mice, Mice, Inbred C57BL, Nitric Oxide metabolism, Oleic Acid, Plant Oils, Sunflower Oil, Vascular Remodeling drug effects, Arteries drug effects, Dietary Fats pharmacology, Fatty Acids, Monounsaturated pharmacology, Vascular Stiffness drug effects
Abstract

Vegetable oils such as palm oil (enriched in saturated fatty acids, SFA) and high-oleic-acid sunflower oil (HOSO, containing mainly monounsaturated fatty acids, MUFA) have emerged as the most common replacements for trans-fats in the food industry. The aim of this study is to analyze the impact of SFA and MUFA-enriched high-fat (HF) diets on endothelial function, vascular remodeling, and arterial stiffness compared to commercial HF diets. Five-week-old male C57BL6J mice were fed a standard (SD), a HF diet enriched with SFA (saturated oil-enriched Food, SOLF), a HF diet enriched with MUFA (unsaturated oil-enriched Food, UOLF), or a commercial HF diet for 8 weeks. Vascular function was analyzed in the thoracic aorta. Structural and mechanical parameters were assessed in mesenteric arteries by pressure myography. SOLF, UOLF, and HF diet reduced contractile responses to phenylephrine and induced endothelial dysfunction in the thoracic aorta. A significant increase in the β-index, and thus in arterial stiffness, was also detected in mesenteric arteries from the three HF groups, due to enhanced deposition of collagen in the vascular wall. SOLF also induced hypotrophic inward remodeling. In conclusion, these data demonstrate a deleterious effect of HF feeding on obesity-related vascular alterations that is exacerbated by SFA.

Published
2021
Full Text
View/download PDF

43. Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension.

Author

Gutiérrez-Arzapalo PY, Rodríguez-Rodríguez P, Ramiro-Cortijo D, Gil-Ortega M, Somoza B, de Pablo ÁLL, González MDC, and Arribas SM

Abstract

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague-Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.

Published
2020
Full Text
View/download PDF

44. Impact of caloric restriction on AMPK and endoplasmic reticulum stress in peripheral tissues and circulating peripheral blood mononuclear cells from Zucker rats.

Author

Vega-Martín E, González-Blázquez R, Manzano-Lista FJ, Martín-Ramos M, García-Prieto CF, Viana M, Rubio MA, Calle-Pascual AL, Lionetti L, Somoza B, Fernández-Alfonso MS, Alcalá M, and Gil-Ortega M

Subjects
Adipocytes metabolism, Adipose Tissue metabolism, Animals, Body Weight, Lipid Metabolism, Liver metabolism, Male, Obesity metabolism, Phosphorylation, Rats, Rats, Zucker, AMP-Activated Protein Kinases metabolism, Caloric Restriction, Endoplasmic Reticulum Stress, Leukocytes, Mononuclear metabolism
Abstract

The activation of endoplasmic reticulum (ER) stress and a reduction of AMP-dependent protein kinase (AMPK) phosphorylation have been described in obesity. We hypothesize that a moderate caloric restriction (CR) might contribute to reducing ER stress and increasing AMPK phosphorylation in peripheral tissues from genetically obese Zucker fa/fa rats and in peripheral blood mononuclear cells (PBMCs). Zucker Lean and Zucker fa/fa rats were fed with chow diet either ad libitum (AL) (C, as controls) or 80% of AL (CR) for 2 weeks, giving rise to four experimental groups: Lean C, Lean CR, fa/fa C and fa/fa CR. CR significantly increased AMPK phosphorylation in the liver, perirenal adipose tissue (PRAT) and PBMCs from fa/fa rats but not in the subcutaneous AT (SCAT), suggesting a reduced response of SCAT to CR. Liver samples of fa/fa rats exhibited an increased mRNA expression of PERK, EIF-2α, XBP-1(s), Chop and caspase 3, which was significantly reduced by CR. PRAT exhibited an overexpression of Edem and PDIA-4 in fa/fa rats, but only PDIA-4 expression was reduced by CR. eIF-2α phosphorylation was significantly increased in all studied tissues from fa/fa rats and reduced by CR. A negative correlation was detected between p-AMPK and p-eIF-2α in the liver, PRAT and PBMCs from fa/fa rats but not in SCAT. This study shows that a moderate CR reduces ER stress and improves AMPK phosphorylation in several peripheral tissues and in circulating PBMCs, suggesting that alterations observed in PBMCs could reflect metabolic alterations associated with obesity., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
Full Text
View/download PDF

45. Relevance of control diet choice in metabolic studies: impact in glucose homeostasis and vascular function.

Author

González-Blázquez R, Alcalá M, Fernández-Alfonso MS, Villa-Valverde P, Viana M, Gil-Ortega M, and Somoza B

Subjects
Acetylcholine pharmacology, Adiposity drug effects, Animals, Aorta, Thoracic drug effects, Biological Availability, Body Weight drug effects, Carbohydrate Metabolism drug effects, Cholesterol metabolism, Diet, Fat-Restricted, Dietary Fiber pharmacology, Fatty Acids, Unsaturated pharmacology, Glucose administration & dosage, Insulin pharmacology, Lipid Metabolism drug effects, Male, Mice, Inbred C57BL, Nitric Oxide metabolism, Phenylephrine metabolism, Solubility, Subcutaneous Fat drug effects, Vasodilation drug effects, Aorta, Thoracic physiology, Diet, Glucose metabolism, Homeostasis
Abstract

The experimental approach for the study of cardiometabolic disorders requires the use of animal models fed with commercial diets whose composition differs notably, even between diets used for control groups. While chow diets are usually made of agricultural by-products, purified low-fat diets (LF) contain a higher percentage of easy metabolizable carbohydrates, together with a reduced amount of polyunsaturated fatty acids, micronutrients and fiber, all associated with metabolic and vascular dysfunction. We hypothesize that the LF diet, commonly used in control animals, could promote adverse vascular and metabolic outcomes. To address this issue, 5-week-old male C57BL6J mice were fed with a standard (Chow) or a LF diet for 6 weeks. Changes in body weight, adiposity, biochemical parameters, systemic and aortic insulin sensitivity and endothelial function were recorded. LF diet did not modify body weight but significantly impaired systemic glucose tolerance and increased triglycerides and cholesterol levels. Endothelial function and aortic insulin sensitivity were significantly impaired in the LF group, due to a reduction of NO availability. These findings highlight the importance of selecting the proper control diet in metabolic studies. It may also suggest that some cardiometabolic alterations obtained in experimental studies using LF as a control diet may be underestimated.

Published
2020
Full Text
View/download PDF

46. Finerenone Reduces Intrinsic Arterial Stiffness in Munich Wistar Frömter Rats, a Genetic Model of Chronic Kidney Disease.

Author

Gil-Ortega M, Vega-Martín E, Martín-Ramos M, González-Blázquez R, Pulido-Olmo H, Ruiz-Hurtado G, Schulz A, Ruilope LM, Kolkhof P, Somoza B, Kreutz R, and Fernández-Alfonso MS

Subjects
Animals, Cardiovascular Diseases etiology, Disease Models, Animal, Endothelium, Vascular drug effects, Endothelium, Vascular pathology, Humans, Kidney blood supply, Kidney drug effects, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Mesenteric Arteries pathology, Oxidative Stress drug effects, Rats, Rats, Wistar, Renal Insufficiency, Chronic urine, Signal Transduction drug effects, Albuminuria drug therapy, Cardiovascular Diseases prevention & control, Mineralocorticoid Receptor Antagonists administration & dosage, Naphthyridines administration & dosage, Renal Insufficiency, Chronic complications, Vascular Stiffness drug effects
Abstract

Background: Development of albuminuria and arterial stiffness in Munich Wistar Frömter (MWF) rats, a model of chronic kidney disease, is related to alterations in extracellular matrix, increased oxidative stress, and endothelial dysfunction. Finerenone (FIN), a novel, nonsteroidal, potent, and selective mineralocorticoid receptor antagonist, improves endothelial dysfunction through enhancing nitric oxide (NO) bioavailability and decreasing superoxide anion levels due to an upregulation in vascular and renal superoxide dismutase activity. We hypothesize that FIN reduces arterial stiffness in this model associated to the reduction in albuminuria and matrix metalloproteinase (MMP)-2/9 activity., Methods: Twelve-week-old MWF rats with established albuminuria and age-matched normoalbuminuric Wistar (W) rats were treated with FIN (10 mg/kg/day, once-daily oral gavage) or with vehicle (control, C) for 4 weeks., Results: Arterial stiffness was significantly higher in mesenteric arteries (MA) of MWF-C as compared to W-C. FIN treatment significantly lowered β-index, a measure of intrinsic stiffness independent of geometry, in MWF (βMWF-FIN = 7.7 ± 0.4 vs. βMWF-C = 9.2 ± 0.5, p < 0.05) positively correlating with urinary albumin excretion. Elastin fenestrae area in the internal elastic lamina of MA from MWF-FIN was significantly larger (+377%, p < 0.05). FIN increased plasma pro-MMP-2 and decreased plasma MMP-2 and MMP-9 activities, correlating with reductions in β-index. MA from MWF-FIN exhibited higher NO bioavailability and reduced superoxide anion levels compared to MWF-C., Conclusion: FIN treatment reduces intrinsic arterial stiffness in MA from MWF rats associated with changes in elastin organization, normalization of MMP-2 and MMP-9 activities, and reduction of oxidative stress. Moreover, reduction of arterial stiffness correlates with reduction in albuminuria., (© 2020 S. Karger AG, Basel.)

Published
2020
Full Text
View/download PDF

47. Caloric restriction induces H 2 O 2 formation as a trigger of AMPK-eNOS-NO pathway in obese rats: Role for CAMKII.

Author

García-Prieto CF, Gil-Ortega M, Plaza A, Manzano-Lista FJ, González-Blázquez R, Alcalá M, Rodríguez-Rodríguez P, Viana M, Aránguez I, Gollasch M, Somoza B, and Fernández-Alfonso MS

Subjects
AMP-Activated Protein Kinases metabolism, Animals, Aorta, Thoracic metabolism, Aorta, Thoracic pathology, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Catalase genetics, Catalase metabolism, Deoxyglucose pharmacology, Endothelial Cells cytology, Endothelial Cells drug effects, Endothelial Cells metabolism, Gene Expression Regulation, Male, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Obesity metabolism, Obesity pathology, Rats, Rats, Zucker, Signal Transduction, Superoxide Dismutase genetics, Superoxide Dismutase metabolism, Superoxides metabolism, Vasodilation, AMP-Activated Protein Kinases genetics, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Caloric Restriction, Hydrogen Peroxide metabolism, Nitric Oxide Synthase Type III genetics, Obesity genetics
Abstract

Caloric restriction (CR) improves endothelial function through the upregulation of adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Moreover, hydrogen peroxide (H 2 O 2 ) is upregulated in yeast subjected to CR. Our aim was to assess if mild short-term CR increases vascular H 2 O 2 formation as a link with AMPK and eNOS activation. Twelve-week old Zucker obese (fa/fa) and control Zucker lean male rats were fed a standard chow either ad libitum (AL, n=10) or with a 20% CR (CR, n=10) for two weeks. CR significantly improved relaxation to ACh in fa/fa rats because of an enhanced endogenous production of H 2 O 2 in aortic rings (H 2 O 2 levels fa/faAL =0.5 ± 0.05 nmol/mg vs. H 2 O 2 levels fa/faCR =0.76 ± 0.07 nmol/mg protein; p<0.05). Expression of mitochondrial superoxide dismutase (Mn-SOD) and total SOD activity were increased in aorta from fa/fa animals after CR. In cultured aortic endothelial cells, serum deprivation or 2-deoxy-d-glucose induced a significant increase in: i) superoxide anion and H 2 O 2 levels, ii) p-AMPK/AMPK and p-eNOS/eNOS expression and iii) nitric oxide levels. This effect was reduced by catalase and strongly inhibited by Ca 2+ /calmodulin-dependent kinase II (CamkII) silencing. In conclusion, we propose that mild short-term CR might be a trigger of mechanisms aimed at protecting the vascular wall by the increase of H 2 O 2 , which then activates AMPK and nitric oxide release, thus improving endothelium-dependent relaxation. In addition, we demonstrate that CAMKII plays a key role in mediating CR-induced AMPK activation through H 2 O 2 increase., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
Full Text
View/download PDF

48. Beneficial Effect of Bariatric Surgery on Abnormal MMP-9 and AMPK Activities: Potential Markers of Obesity-Related CV Risk.

Author

García-Prieto CF, Gil-Ortega M, Vega-Martín E, Ramiro-Cortijo D, Martín-Ramos M, Bordiú E, Sanchez-Pernaute A, Torres A, Aránguez I, Fernández-Alfonso M, Rubio MA, and Somoza B

Abstract

Bariatric surgery (BS) results in sustained weight loss and may reverse inflammation, metabolic alterations, extracellular matrix remodeling and arterial stiffness. We hypothesize that increased stiffening in omental arteries from obese patients might be associated with an increase in MMP activity and a decrease in p-AMPK, together with systemic oxidative stress and inflammation. Moreover, BS could contribute to reversing these alterations. This study was conducted with 38 patients of Caucasian origin: 31 adult patients with morbid obesity (9 men and 22 women; mean age 46 years and BMI = 42.7 ± 1.0 kg/m 2 ) and 7 non-obese subjects (7 women; mean age 45 years and BMI = 22.7 ± 0.6 kg/m 2 ). Seventeen obese patients were studied before and 12 months after BS. The stiffness index β, an index of intrinsic arterial stiffness, was determined in omental arteries and was significantly higher in obese patients. Levels of phosphorylated AMPK (p-AMPK Thr-172 ) and SIRT-1 were significantly lower in peripheral blood mononuclear cells (PBMCs) from obese patients than those from non-obese patients ( p < 0.05) and were normalized after BS. Total and active MMP-9 activities, LDH, protein carbonyls and uric acid were higher in obese patients and reduced by BS. Moreover, there was a correlation between plasmatic LDH levels and the stiffness index β. BS has a beneficial effect on abnormal MMP-9, LDH and AMPK activities that might be associated with the development of arterial stiffness in obese patients. Since these parameters are easily measured in blood samples, they could constitute potential biomarkers of cardiovascular risk in morbid obesity.

Published
2019
Full Text
View/download PDF

49. Beneficial effects of murtilla extract and madecassic acid on insulin sensitivity and endothelial function in a model of diet-induced obesity.

Author

Arancibia-Radich J, González-Blázquez R, Alcalá M, Martín-Ramos M, Viana M, Arribas S, Delporte C, Fernández-Alfonso MS, Somoza B, and Gil-Ortega M

Subjects
Animals, Aorta metabolism, Disease Models, Animal, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Insulin pharmacology, Insulin Resistance, Male, Mice, Mice, Inbred C57BL, Myrtaceae metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Obesity metabolism, Phosphorylation, Plant Extracts chemistry, Plant Extracts metabolism, Plant Leaves chemistry, Plant Leaves metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 1 antagonists & inhibitors, Protein Tyrosine Phosphatase, Non-Receptor Type 1 genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 1 metabolism, Proto-Oncogene Proteins c-akt metabolism, Triterpenes chemistry, Triterpenes metabolism, Diet, High-Fat, Endothelium, Vascular drug effects, Myrtaceae chemistry, Obesity pathology, Plant Extracts pharmacology, Triterpenes pharmacology
Abstract

Infusions of murtilla leaves exhibit antioxidant, analgesic, and anti-inflammatory properties. Several compounds that are structurally similar to madecassic acid (MA), a component of murtilla leaf extract (ethyl acetate extract, EAE), have been shown to inhibit protein tyrosine phosphatase 1B (PTP1P). The aim of this study was to evaluate if EAE and two compounds identified in EAE (MA and myricetin [MYR]) could have a beneficial effect on systemic and vascular insulin sensitivity and endothelial function in a model of diet-induced obesity. Experiments were performed in 5-week-old male C57BL6J mice fed with a standard (LF) or a very high-fat diet (HF) for 4 weeks and treated with EAE, MA, MYR, or the vehicle as control (C). EAE significantly inhibited PTP1B. EAE and MA, but not MYR, significantly improved systemic insulin sensitivity in HF mice and vascular relaxation to Ach in aorta segments, due to a significant increase of eNOS phosphorylation and enhanced nitric oxide availability. EAE, MA, and MYR also accounted for increased relaxant responses to insulin in HF mice, thus evidencing that the treatments significantly improved aortic insulin sensitivity. This study shows for the first time that EAE and MA could constitute interesting candidates for treating insulin resistance and endothelial dysfunction associated with obesity.

Published
2019
Full Text
View/download PDF

50. Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress.

Author

González-Blázquez R, Somoza B, Gil-Ortega M, Martín Ramos M, Ramiro-Cortijo D, Vega-Martín E, Schulz A, Ruilope LM, Kolkhof P, Kreutz R, and Fernández-Alfonso MS

Abstract

Albuminuria is an early marker of renovascular damage associated to an increase in oxidative stress. The Munich Wistar Frömter (MWF) rat is a model of chronic kidney disease (CKD), which exhibits endothelial dysfunction associated to low nitric oxide availability. We hypothesize that the new highly selective, non-steroidal mineralocorticoid receptor (MR) antagonist, finerenone, reverses both endothelial dysfunction and microalbuminuria. Twelve-week-old MWF (MWF-C; MWF-FIN) and aged-matched normoalbuminuric Wistar (W-C; W-FIN) rats were treated with finerenone (FIN, 10 mg/kg/day p.o.) or vehicle (C) for 4-week. Systolic blood pressure (SBP) and albuminuria were determined the last day of treatment. Finerenone lowered albuminuria by >40% and significantly reduced SBP in MWF. Aortic rings of MWF-C showed higher contractions to either noradrenaline (NA) or angiotensin II (Ang II), and lower relaxation to acetylcholine (Ach) than W-C rings. These alterations were reversed by finerenone to W-C control levels due to an upregulation in phosphorylated Akt and eNOS, and an increase in NO availability. Apocynin and 3-amino-1,2,4-triazole significantly reduced contractions to NA or Ang II in MWF-C, but not in MWF-FIN rings. Accordingly, a significant increase of Mn-superoxide dismutase (SOD) and Cu/Zn-SOD protein levels were observed in rings of MWF-FIN, without differences in p22phox, p47phox or catalase levels. Total SOD activity was increased in kidneys from MWF-FIN rats. In conclusion, finerenone improves endothelial dysfunction through an enhancement in NO bioavailability and a decrease in superoxide anion levels due to an upregulation in SOD activity. This is associated with an increase in renal SOD activity and a reduction of albuminuria.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results