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22 results on '"Sommer, Natascha"'

1. Estimated plasma volume status: association with congestion, cardiorenal syndrome and prognosis in precapillary pulmonary hypertension

Author

Yogeswaran, Athiththan, Richter, Manuel J., Husain-Syed, Faeq, Rako, Zvonimir, Sommer, Natascha, Grimminger, Friedrich, Seeger, Werner, Ghofrani, Hossein Ardeschir, Gall, Henning, Tello, Khodr, and Justus Liebig University Giessen

Subjects
glomerular filtration rate, ddc:610, pulmonary arterial hypertension, survival, fluid balance, chronic thromboembolic pulmonary hypertension
Abstract

Background: Volume overload is often associated with clinical deterioration in precapillary pulmonary hypertension (PH). However, thorough assessment of volume overload is complex and therefore not routinely performed. We examined whether estimated plasma volume status (ePVS) is associated with central venous congestion and prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH) or chronic thromboembolic PH (CTEPH). Methods: We included all patients with incident IPAH or CTEPH enrolled in the Giessen PH Registry between January 2010 and January 2021. Plasma volume status was estimated using the Strauss formula. Results: In total, 381 patients were analyzed. Patients with high ePVS (≥4.7 vs.

Published
2023
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2. Alternative Oxidase Attenuates Cigarette Smoke-induced Lung Dysfunction and Tissue Damage

Author

Giordano, Luca, Farnham, Antoine, Dhandapani, Praveen K., Salminen, Laura, Bhaskaran, Jahnavi, Voswinckel, Robert, Rauschkolb, Peter, Scheibe, Susan, Sommer, Natascha, Beisswenger, Christoph, Weissmann, Norbert, Braun, Thomas, Jacobs, Howard T., Bals, Robert, Herr, Christian, Szibor, Marten, Institute of Biotechnology, University of Helsinki, Genetics, and Research Programme for Molecular Neurology

Subjects
cigarette smoke, EMPHYSEMA, DEFECTS, CONTRIBUTES, MECHANISMS, MODEL, mitochondria, alternative oxidase, CELL-DEATH, SPUTUM, 3121 General medicine, internal medicine and other clinical medicine, COPD, MMP-9
Abstract

Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain. AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months. It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS). In contrast, the early-phase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected. The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage, mitochondrial ROS production, and lung remodeling. Our findings implicate mitochondrial respiratory inhibition as a key pathogenic mechanism of CS toxicity in the lung. We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage.

Published
2022
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3. Additional file 1 of Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension

Author

Eichstaedt, Christina A., Saßmannshausen, Zoe, Shaukat, Memoona, Cao, Ding, Xanthouli, Panagiota, Gall, Henning, Sommer, Natascha, Ghofrani, Hossein-Ardeschir, Seyfarth, Hans-Jürgen, Lerche, Marianne, Halank, Michael, Kleymann, Janina, Benjamin, Nicola, Harutyunova, Satenik, Egenlauf, Benjamin, Milger, Katrin, Rosenkranz, Stephan, Ewert, Ralf, Klose, Hans, Hoeper, Marius M., Olsson, Karen M., Lankeit, Mareike, Lange, Tobias J., Hinderhofer, Katrin, and Grünig, Ekkehard

Abstract

Additional file 1: Table S1. (Likely) pathogenic BMPR2 variants identified in the cohort.

Published
2022
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5. Mitochondrial physiology: Gnaiger Erich et al ― MitoEAGLE Task Group

Author

Gnaiger, Erich, Aasander Frostner, Eleonor, Abdul Karim, Norwahidah, Abdel-Rahman, Engy Ali, Abumrad, Nada A, Acuna-Castroviejo, Dario, Adiele, Reginald C, Ahn, Bumsoo, Alencar, MB, Ali, Sameh S, Almeida, Angeles, Alton, Lesley, Alves, Marco G, Amati, Francesca, Amoedo, Nivea Dias, Amorim, Ricardo, Anderson, Ethan J, Andreadou, Ioanna, Antunes, Diana, Arago, Marc, Aral, Cenk, Arandarcikaite, Odeta, Arias-Reyes, Christian, Armand, Anne-Sophie, Arnould, Thierry, Avram, Vlad Florian, Axelrod, Christopher L, Bairam, Aida, Bailey, Damian M, Bajpeyi, Sudip, Bajzikova, Martina, Bakker, Barbara M, Barlow, Jonathan, Bardal, Tora, Banni, A, Bastos Sant'Anna Silva, Ana Carolina, Batterson, Philip, Battino, Maurizio, Bazil, Jason, Beard, Daniel A, Beleza, Jorge, Bednarczyk, Piotr, Bello, Fiona, Ben-Shachar, Dorit, Bento Guida, Jose Freitas, Bergdahl, Andreas, Berge, Rolf K, Bergmeister, Lisa, Bernardi, Paolo, Berridge, Michael V, Bettinazzi, Stefano, Bishop, David, Blier, Pierre U, Blindheim, Dan Filip, Boardman, Neoma T, Boetker, Hans Erik, Borchard, Sabine, Boros, Mihaly, Borsheim, Elisabet, Borras, Consuelo, Borutaite, Vilma, Botella, Javier, Bouillaud, Frederic, Bouitbir, Jamal, Boushel, Robert C, Bovard, Josh, Bravo-Sagua, Roberto, Breton, Sophie, Brown, David A, Brown, Guy C, Brown, Robert A, Brozinick, Joseph T, Buettner, Garry R, Burtscher, Johannes, Bustos, Matilde, Calabria, Elisa, Calbet, Jose A, Calzia, Enrico, Cannon, Daniel T, Cano Sanchez, Maria, Canto Alvarez, Carles, Cardinale, D, Cardoso, Luiza Helena Daltro, Carvalho, Eugenia, Casado Pinna, Marta, Cassar, Samantha, Castelo, Maria P, Castilho, Roger F, Cavalcanti-de-Albuquerque, Joao Paulo, Cecatto, Cristiane, Celen, Murat C, Cervinkova, Zuzana, Chabi, Beatrice, Chakrabarti, Lisa, Chakrabarti, Sasanka, Chaurasia, Bhagirath, Chen, Quan, Chicco, Adam J, Chinopoulos, Christos, Chowdhury, Subir K, Cizmarova, Beata, Clementi, Emilio, Coen, Paul M, Cohen, Bruce H, Coker, Robert H, Collin-Chenot, Anne, Coughlan, Melinda T, Coxito, Petro, Crisostomo, Luis, Crispim, Marcell, Crossland, Hannah, Dahdah, Norma, Dalgaard, Louise T, Dambrova, Maija, Danhelovska, Tereza, Darveau, Charles A, Darwin, Paula M, Das, Anibh M, Dash, Ranjan K, Davidova, Eliska, Davis, Michael S, Dayanidhi, Sudarshan, De Bem, Andreza Fabro, De Goede, Paul, De Palma, Clara, De Pinto, Vito, Dela, F, Dembinska-Kiec, Aldona, Detraux, Damien, Devaux, Yvan, Di Marcello, Marco, Di Paola, Floriana Jessica, Dias, Candida, Dias, Tania R, Diederich, Marc, Distefano, Giovanna, Djafarzadeh, Siamak, Doermann, Niklas, Doerrier, Carolina, Dong, Lan-Feng, Donnelly, Chris, Drahota, Zdenek, Duarte, Filipe Valente, Dubouchaud, Herve, Duchen, Michael R, Dumas, Jean-Francois, Durham, William J, Dymkowska, Dorota, Dyrstad, Sissel E, Dyson, Alex, Dzialowski, Edward M, Eaton, Simon, Ehinger, Johannes, Elmer, Eskil, Endlicher, Rene, Engin, Ayse B, Escames, Germaine, Evinova, Andrea, Ezrova, Zuzana, Falk, Marni Joy, Fell, David A, Ferdinandy, Peter, Ferko, Miroslav, Fernandez-Ortiz, Marisol, Erika, Fernandez-Vizarra, Ferreira, Julio Cesar Batista, Ferreira, Rita, Ferri, Alessandra, Festuccia, WT, Fessel, Joshua P, Filipovska, Aleksandra, Fisar, Zdenek, Fischer, Christine, Fischer, Michael, Fisher, Gordon, Fisher, Joshua J, Fontanesi, Flavia, Forbes-Hernandez, Tamara Y, Ford, Ellen, Fornaro, Mara, Fuertes Agudo, Marina, Fulton, Montana, Galina, Antonio, Galkin, Alexander, Gallee, Leon, Galli, Gina L, Gama Perez, Pau, Gan, Zhenji, Ganetzky, Rebecca, Gao, Yun, Garcia, Geovana S, Garcia-Rivas, Gerardo, Garcia-Roves, Pablo Miguel, Garcia-Souza, Luiz Felipe, Garlid, Keith D, Garrabou, Gloria, Garten, Antje, Gastaldelli, Amalia, Gayen, Jiaur, Genders, Amanda J, Genova, Maria Luisa, Giampieri, Francesca, Glatz, Jan FC, Giovarelli, Matteo, Goikoetxea Usandizaga, Naroa, Goncalo Teixeira da Silva, Rui, Goncalves, Debora Farina, Gonzalez-Armenta, Jenny L, Gonzalez-Francesqua, A, Gonzalez-Freire, Marta, Gonzalo, Hugo, Goodpaster, Bret H, Gorr, Thomas A, Gourlay, Campbell W, Grams, Bente, Granata, Cesare, Grefte, Sander, Grilo, Luis, Guarch, Meritxell Espino, Gueguen, Naig, Gumeni, Sentiljana, Haas, Clarissa B, Haavik, Jan, Hachmo, Yafit, Haendeler, Judith, Haider, Markus, Hajrulahovic, Anesa, Hamann, Andrea, Han, Jin, Han, Woo Hyun, Hancock, Chad R, Hand, Steven C, Handl, Jiri, Hansikova, Hana, Hardee, Justin P, Hargreaves, Ian P, Harper, Mary Ellen, Harrison, David K, Hassan, Hazirah, Hatakova, Zuzana, Hausenloy, Derek J, Heales, Simon JR, Heiestad, Christina, Hellgren, Kim T, Henrique, Alexandrino, Hepple, Russell T, Hernansanz-Agustin, Pablo, Hewakapuge, Sudinna, Hickey, Anthony J, Ho, Dieu Hien, Hoehn, Kyle L, Hoel, Frederik, Holland, Olivia J, Holloway, Graham P, Holzner, Lorenz, Hoppel, Charles L, Hoppeler, H, Hoppel, Florian, Houstek, Josef, Huete-Ortega, Maria, Hyrossova, Petra, Iglesias-Gonzalez, Javier, Indiveri, Cesare, Irving, Brian A, Isola, Raffaella, Iyer, Shilpa, Jackson, Christophe B, Jadiya, Pooja, Jana, Prado Fabian, Jandeleit-Dahm, K, Jang, David H, Jang, Young C, Janowska, Joanna, Jansen, Kirsten, Jansen-Duerr, Pidder, Jansone, Baiba, Jarmuszkiewicz, Wieslawa, Jaskiewicz, Anna, Jaspers, Richard T, Jedlicka, Jan, Jerome, Estaquier, Jespersen, Nichlas R, Jha, Rajan K, Joseph, Vincent, Juhasz, Laszlo, Jurczak, Michael J, Jurk, Diana, Kaambre, Tuuli, Kaczor, Jan J, Kainulainen, Heikki, Kampa, Rafal Pawel, Kandel, Sunil M, Kane, Daniel A, Kapferer, Werner, Kapnick, Senta, Kappler, Lisa, Karabatsiakis, Alexander, Karavaeva, Iuliia, Karkucinska-Wieckowska, Agnieszka, Kaur, Sarbjot, Keijer, Jaap, Keller, Markus A, Keppner, Gloria, Khamoui, Andy V, Kidere, Dita, Kilbaugh, Todd, Kim, Hyoung Kyu, Kim, Julian KS, Kimoloi, Sammy, Klepinin, Aleksandr, Klepinina, Lyudmila, Klingenspor, Martin, Klocker, Helmut, Komlódi, Timea, Kolasa, Iris, Koopman, Werner JH, Kopitar-Jerala, Natasa, Kowaltowski, Alicia J, Kozlov, Andrey V, Krajcova, Adela, Krako Jakovljevic, Nina, Kristal, Bruce S, Krycer, Jamer R, Kuang, Jujiao, Kucera, Otto, Kuka, Janis, Kwak, Hyo Bum, Kwast, Kurt, Kwon, Oh Sung, Laasmaa, Martin, Labieniec-Watala, Magdalena, Lai, Nicola, Lalic, Nebojsa M, Land, John M, Lane, Nick, Laner, Verena, Lanza, Ian R, Laouafa, Sofien, Larsen, Steen, Larsen, Terje S, Lavery, Gareth G, Lazou, Antigone, Ledo, Ana Margarida, Lee, Hong Kyu, Leeuwenburgh, Christiaan, Lehti, Maarit, Lemieux, Helene, Lenaz, Giorgio, Lerfall, Jorgen, Li, Pingan A, Li Puma, Lance, Liang, Liping, Liepins, Edgars, Lin, Chien-Te, Liu, Jiankang, Lopez, Luis C, Lucchinetti, Eliana, Ma, Tao, Macedo, Maria P, Machado, Ivo F, Maciej, Sarah, MacMillan-Crow, Lee Ann, Magalhaes, Jose, Magri, Andrea, Majtnerova, Pavlina, Makarova, Elina, Makrecka-Kuka, Marina, Malik, Afshan N, Marcouiller, Francois, Marechal, Amandine, Markova, Michaela, Markovic, Ivanka, Martin, Daniel S, Martins, Ana Dias, Martins, Joao D, Maseko, Tumisang Edward, Maull, Felicia, Mazat, Jean Pierre, McKenna, Helen T, McKenzie, Matthew, McMillan, Duncan GG, McStay, Gavin P, Menze, Michael A, Mendham, Amy, Mercer, John R, Merz, Tamara, Messina, Angela, Meszaros, Andras T, Methner, Axel, Michalak, Slawomir, Mila Guasch, Maria, Minuzzi, Luciele M, Misirkic Marjanovic, Maja, Moellering, Douglas R, Moisoi, Nicoleta, Molina, Anthony JA, Montaigne, David, Moore, Anthony L, Moore, Christy, Moreau, Kerrie, Moreira, Bruno P, Moreno-Sanchez, Rafael, Mracek, Tomas, Muccini, Anna Maria, Muntane, Jordi, Muntean, Danina M, Murray, Andrew J, Musiol, Eva, Nabben, Miranda, Nair, K Sreekumaran, Nehlin, Jan O, Nemec, Michal, Nesci, Salvatore, Neufer, P Darrell, Neuzil, Jiri, Neviere, Remi, Newsom, Sean A., Norman, Jennifer, Nozickova, Katerina, Nunes, Sara, Nuoffer, Jean-Marc, O'Brien, Kristin, O'Brien, Katie A, O'Gorman, Donal, Olgar, Yusuf, Oliveira, Ben, Oliveira, Jorge, Oliveira, Marcus F, Oliveira, Marcos Tulio, Oliveira, Pedro F, Oliveira, Paulo J, Olsen, Rolf Erik, Orynbayeva, Zulfiya, Osiewacz, Heinz D, Paez, Hector, Pak, Youngmi K, Pallotta, Maria L, Palmeira, Carlos M, Parajuli, Nirmala, Passos, Joao F, Passrugger, Manuela, Patel, Hemal H, Pavlova, Nadia, Pavlovic, Kasja, Pecina, Petr, Pedersen, Tina M, Perales, Jose Carlos, Pereira da Silva Grilo da Silva, Filomena, Pereira, Rita, Perez Valencia, Juan A, Perks, Kara L, Pesta, Dominik, Petit, Patrice X, Pettersen Nitschke, Ina Katrine, Pichaud, Nicolas, Pichler, Irene, Piel, Sarah, Pietka, Terri A, Pinho, Sonia A, Pino, Maria F, Pirkmajer, Sergej, Place, Nicolas, Plangger, Mario, Porter, Craig, Porter, Richard K, Preguica, Ines, Procaccio, Vincent, Prochownik, Edward V, Prola, Alexandre, Pulinilkunnil, Thomas, Puskarich, Michael A, Puurand, Marju, Radenkovic, Filip, Ramzan, Rabia, Rattan, Suresh IS, Reano, Simone, Reboredo, Patricia, Rees, Bernard B, Renner-Sattler, Kathrin, Rial, Eduardo, Robinson, Matthew M, Roden, Michael, Rodrigues, Ana Sofia, Rodriguez, Enrique, Rodriguez-Enriquez, Sara, Roesland, Gro Vatne, Rolo, Anabela Pinto, Ropelle, Eduardo R, Roshanravan, Baback, Rossignol, Rodrigue, Rossiter, Harry B, Rousar, Tomas, Rubelj, Ivica, Rybacka-Mossakowska, Joanna, Saada, Ann, Safaei, Zahra, Sarlak, Saharnaz, Salin, Karine, Salvadego, Desy, Sandi, Carmen, Saner, Nicholas, Santos, Diana, Sanz, Alberto, Sardao, Vilma, Sazanov, Leonid A, Scaife, Paula, Scatena, Roberto, Schartner, Melanie, Scheibye-Knudsen, Morten, Schilling, Jan M, Schlattner, Uwe, Schmitt, Sabine, Schneider Gasser, Edith Mariane, Schoenfeld, Peter, Schots, Pauke C, Schulz, Rainer, Schwarzer, Christoph, Scott, Graham R, Selman, Colin, Sendon, Pamella Marie, Shabalina, Irina G, Sharma, Pushpa, Sharma, Vipin, Shevchuk, Igor, Shirazi, Reza, Shiroma, Jonathan G, Siewiera, Karolina, Silber, Ariel M, Silva, Ana Maria, Sims, Carrie A, Singer, Dominique, Singh, Brijesh Kumar, Skolik, Robert A, Smenes, Benedikte Therese, Smith, James, Soares, Félix Alexandre Antunes, Sobotka, Ondrej, Sokolova, Inna, Solesio Torregrosa, M De la Encarnacion, Soliz, Jorge, Sonkar, Vijay K, Sova, Marina, Sowton, Alice P, Sparagna, Genevieve C, Sparks, Lauren M, Spinazzi, Marco, Stankova, Pavla, Starr, Jonathan, Stary, Creed, Stefan, Eduard, Stelfa, Gundega, Stepto, Nigel K, Stevanovic, Jelena, Stiban, Johnny, Stier, Antoine, Stocker, Roland, Storder, Julie, Sumbalova, Zuzana, Suomalainen, Wartiovaara Anu, Suravajhala, Prashanth, Svalbe, Baiba, Swerdlow, Russel H, Swiniuch, Daria, Szabo, Ildiko, Szewczyk, Adam, Szibor, Marten, Tanaka, Masashi, Tandler, Bernard, Tarnopolsky, Mark A, Tausan, Daniel, Tavernarakis, Nektarios, Tepp, Kersti, Teodoro, J, Thakkar, Himani, Thapa, Maheshwo, Thyfault, John P, Tomar, Dhanendra, Ton, Riccardo, Torp, May-Kristin, Torres-Quesada, Omar, Towheed, Atif, Treberg, Jason R, Tretter, Laszlo, Trewin, Adam J, Trifunovic, Aleksandra, Trivigno, Catherine, Tronstad, Karl Johan, Trougakos, Ioannis P, Truu, Laura, Tuncay, Erkan, Turan, Belma, Tyrrell, Daniel J, Urban, Tomas, Urner, Sofia, Valentine, Joseph Marco, Van Bergen, Nicole J, Van der Ende, Miranda, Varricchio, Frederick, Vaupel, Peter, Vella, Joanna, Vendelin, Marko, Verdaguer, IB, Vercesi, Anibal E, Vernerova, Andrea, Victor, Victor Manuel, Vieira Ligo Teixeira, Camila, Vidimce, Josif, Viel, Christian, Vieyra, Adalberto, Vilks, Karlis, Villena, Joseph A, Vincent, Vinnyfred, Vinogradov, Andrey D, Viscomi, Carlo, Vitorino, Rui Miguel Pinheiro, Vlachaki Walker, Julia, Vogt, Sebastian, Volani, Chiara, Volska, Kristine, Votion, Dominique-Marie, Vujacic-Mirski, Ksenija, Wagner, Brett A, Ward, Marie Louise, Warnsmann, Verena, Wasserman, David H, Watala, Cezary, Wei, Yau-Huei, Weinberger, Klaus M, White, Sarah, Whitfield, Jamie, Wickert, Anika, Wieckowski, Mariusz R, Wiesner, Rudolf J, Williams, Caroline M, Winwood-Smith, Hugh, Wohlgemuth, Stephanie E, Wohlwend, Martin, Wolff, Jonci Nikolai, Wrutniak-Cabello, Chantal, Wuest, Rob C I, Yokota, Takashi, Zablocki, Krzysztof, Zanon, Alessandra, Zanou, Nadege, Zaugg, Kathrin, Zaugg, Michael, Zdrazilova, Lucie, Zhang, Yong, Zhang, Yi Zhu, Zikova, Alena, Zischka, Hans, Zorzano, Antonio, Zujovic, Tijana, Zurmanova, Jitka, Zvejniece, Liga, Lagarrigue, Sylviane, Munro, Daniel, Pereira, Susana, Laranjinha, Joäo, Hecker, Matthias, Jusic, Amela, Prigione, Alessandro, Sommer, Natascha, Weissig, Volkmar, Guida, Bento, G, John G, Jones, JG, AMS - Tissue Function & Regeneration, AMS - Rehabilitation & Development, Physiology, Mito-Eagle - Evolution-Age-Gender-Lifestyle-Environment (Mito-Eagle), Oroboros Instruments, Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Gnaiger Erich, Aasander Frostner Eleonor, Abdul Karim Norwahidah, Abdel-Rahman Engy Ali, Abumrad Nada A, Acuna-Castroviejo Dario, Adiele Reginald C, Ahn Bumsoo, Alencar Mayke Bezerra, Ali Sameh S, Almeida Angeles, Alton Lesley, Alves Marco G, Amati Francesca, Amoedo Nivea Dias, Amorim Ricardo, Anderson Ethan J, Andreadou Ioanna, Antunes Diana, Arago Marc, Aral Cenk, Arandarcikaite Odeta, Arias-Reyes Christian, Armand Anne-Sophie, Arnould Thierry, Avram Vlad F, Axelrod Christopher L, Bailey Damian M, Bairam Aida, Bajpeyi Sudip, Bajzikova Martina, Bakker Barbara M, Banni Aml, Bardal Tora, Barlow J, Bastos Sant'Anna Silva Ana Carolina, Batterson Philip M, Battino Maurizio, Bazil Jason N, Beard Daniel A, Bednarczyk Piotr, Beleza Jorge, Bello Fiona, Ben-Shachar Dorit, Bento Guida Jose Freitas, Bergdahl Andreas, Berge Rolf K, Bergmeister Lisa, Bernardi Paolo, Berridge Michael V, Bettinazzi Stefano, Bishop David J, Blier Pierre U, Blindheim Dan Filip, Boardman Neoma T, Boetker Hans Erik, Borchard Sabine, Boros Mihaly, Boersheim Elisabet, Borras Consuelo, Borutaite Vilma, Botella Javier, Bouillaud Frederic, Bouitbir Jamal, Boushel Robert C, Bovard Josh, Bravo-Sagua Roberto, Breton Sophie, Brown David A, Brown Guy C, Brown Robert Andrew, Brozinick Joseph T, Buettner Garry R, Burtscher Johannes, Bustos Matilde, Calabria Elisa, Calbet Jose AL, Calzia Enrico, Cannon Daniel T, Cano Sanchez Maria Consolacion, Canto Alvarez Carles, Cardinale Daniele A, Cardoso Luiza HD, Carvalho Eugenia, Casado Pinna Marta, Cassar Samantha, Castelo Rueda Maria Paulina, Castilho Roger F, Cavalcanti-de-Albuquerque Joao Paulo, Cecatto Cristiane, Celen Murat C, Cervinkova Zuzana, Chabi Beatrice, Chakrabarti Lisa, Chakrabarti Sasanka, Chaurasia Bhagirath, Chen Quan, Chicco Adam J, Chinopoulos Christos, Chowdhury Subir Kumar, Cizmarova Beata, Clementi Emilio, Coen Paul M, Cohen Bruce H, Coker Robert H, Collin-Chenot Anne, Coughlan Melinda T, Coxito Pedro, Crisostomo Luis, Crispim Marcell, Crossland Hannah, Dahdah Norma Ramon, Dalgaard Louise T, Dambrova Maija, Danhelovska Tereza, Darveau Charles-A, Darwin Paula M, Das Anibh Martin, Dash Ranjan K, Davidova Eliska, Davis Michael S, Dayanidhi Sudarshan, De Bem Andreza Fabro, De Goede Paul, De Palma Clara, De Pinto Vito, Dela Flemming, Dembinska-Kiec Aldona, Detraux Damian, Devaux Yvan, Di Marcello Marco, Di Paola Floriana Jessica, Dias Candida, Dias Tania R, Diederich Marc, Distefano Giovanna, Djafarzadeh Siamak, Doermann Niklas, Doerrier Carolina, Dong Lan-Feng, Donnelly Chris, Drahota Zdenek, Duarte Filipe Valente, Dubouchaud Herve, Duchen Michael R, Dumas Jean-Francois, Durham William J, Dymkowska Dorota, Dyrstad Sissel E, Dyson Alex, Dzialowski Edward M, Eaton Simon, Ehinger Johannes K, Elmer Eskil, Endlicher Rene, Engin Ayse Basak, Escames Germaine, Evinova Andrea, Ezrova Zuzana, Falk Marni J, Fell David A, Ferdinandy Peter, Ferko Miroslav, Fernandez-Ortiz Marisol, Fernandez-Vizarra Erika, Ferreira Julio Cesar B, Ferreira Rita Maria P, Ferri Alessandra, Fessel Joshua Patrick, Festuccia William T, Filipovska Aleksandra, Fisar Zdenek, Fischer Christine, Fischer Michael J, Fisher Gordon, Fisher Joshua J, Fontanesi Flavia, Forbes-Hernandez Tamara Y, Ford Ellen, Fornaro Mara, Fuertes Agudo Marina, Fulton Montana, Galina Antonio, Galkin Alexander, Gallee Leon, Galli Gina L J, Gama Perez Pau, Gan Zhenji, Ganetzky Rebecca, Gao Yun, Garcia Geovana S, Garcia-Rivas Gerardo, Garcia-Roves Pablo Miguel, Garcia-Souza Luiz F, Garlid Keith D, Garrabou Gloria, Garten Antje, Gastaldelli Amalia, Gayen Jiaur, Genders Amanda J, Genova Maria Luisa, Giampieri Francesca, Giovarelli Matteo, Glatz Jan FC, Goikoetxea Usandizaga Naroa, Goncalo Teixeira da Silva Rui, Goncalves Debora Farina, Gonzalez- Armenta Jenny L, Gonzalez-Franquesa Alba, Gonzalez-Freire Marta, Gonzalo Hugo, Goodpaster Bret H, Gorr Thomas A, Gourlay Campbell W, Grams Bente, Granata Cesare, Grefte Sander, Grilo Luis, Guarch Meritxell Espino, Gueguen Naig, Gumeni Sentiljana, Haas Clarissa, Haavik Jan, Hachmo Yafit, Haendeler Judith, Haider Markus, Hajrulahovic Anesa, Hamann Andrea, Han Jin, Han Woo Hyun, Hancock Chad R, Hand Steven C, Handl Jiri, Hansikova Hana, Hardee Justin P, Hargreaves Iain P, Harper Mary- Ellen, Harrison David K, Hassan Hazirah, Hatokova Zuzana, Hausenloy Derek J, Heales Simon JR, Hecker Matthias, Heiestad Christina, Hellgren Kim T, Henrique Alexandrino, Hepple Russell T, Hernansanz- Agustin Pablo, Hewakapuge Sudinna, Hickey Anthony J, Ho Dieu Hien, Hoehn Kyle L, Hoel Fredrik, Holland Olivia J, Holloway Graham P, Holzner Lorenz, Hoppel Charles L, Hoppel Florian, Hoppeler Hans, Houstek Josef, Huete-Ortega Maria, Hyrossova Petra, Iglesias-Gonzalez Javier, Indiveri Cesare, Irving Brian A, Isola Raffaella, Iyer Shilpa, Jackson Christopher Benjamin, Jadiya Pooja, Jana Prado Fabian, Jandeleit-Dahm Karin, Jang David H, Jang Young Charles, Janowska Joanna, Jansen Kirsten M, Jansen-Duerr Pidder, Jansone Baiba, Jarmuszkiewicz Wieslawa, Jaskiewicz Anna, Jaspers Richard T, Jedlicka Jan, Jerome Estaquier, Jespersen Nichlas Riise, Jha Rajan Kumar, Jones John G, Joseph Vincent, Juhasz Laszlo, Jurczak Michael J, Jurk Diana, Jusic Amela, Kaambre Tuuli, Kaczor Jan Jacek, Kainulainen Heikki, Kampa Rafal Pawel, Kandel Sunil Mani, Kane Daniel A, Kapferer Werner, Kapnick Senta, Kappler Lisa, Karabatsiakis Alexander, Karavaeva Iuliia, Karkucinska-Wieckowska Agnieszka, Kaur Sarbjot, Keijer Jaap, Keller Markus A, Keppner Gloria, Khamoui Andy V, Kidere Dita, Kilbaugh Todd, Kim Hyoung Kyu, Kim Julian KS, Kimoloi Sammy, Klepinin Aleksandr, Klepinina Lyudmila, Klingenspor Martin, Klocker Helmut, Kolassa Iris, Komlodi Timea, Koopman Werner JH, Kopitar-Jerala Natasa, Kowaltowski Alicia J, Kozlov Andrey V, Krajcova Adela, Krako Jakovljevic Nina, Kristal Bruce S, Krycer James R, Kuang Jujiao, Kucera Otto, Kuka Janis, Kwak Hyo Bum, Kwast Kurt E, Kwon Oh Sung, Laasmaa Martin, Labieniec-Watala Magdalena, Lagarrigue Sylviane, Lai Nicola, Lalic Nebojsa M, Land John M, Lane Nick, Laner Verena, Lanza Ian R, Laouafa Sofien, Laranjinha Joao, Larsen Steen, Larsen Terje S, Lavery Gareth G, Lazou Antigone, Ledo Ana Margarida, Lee Hong Kyu, Leeuwenburgh Christiaan, Lehti Maarit, Lemieux Helene, Lenaz Giorgio, Lerfall Joergen, Li Pingan Andy, Li Puma Lance, Liang Liping, Liepins Edgars, Lin Chien-Te, Liu Jiankang, Lopez Garcia Luis Carlos, Lucchinetti Eliana, Ma Tao, Macedo Maria Paula, Machado Ivo F, Maciej Sarah, MacMillan-Crow Lee Ann, Magalhaes Jose, Magri Andrea, Majtnerova Pavlina, Makarova Elina, Makrecka-Kuka Marina, Malik Afshan N, Marcouiller Francois, Marechal Amandine, Markova Michaela, Markovic Ivanka, Martin Daniel S, Martins Ana Dias, Martins Joao D, Maseko Tumisang Edward, Maull Felicia, Mazat Jean-Pierre, McKenna Helen T, McKenzie Matthew, McMillan Duncan GG, McStay Gavin P, Mendham Amy, Menze Michael A, Mercer John R, Merz Tamara, Messina Angela, Meszaros Andras, Methner Axel, Michalak Slawomir, Mila Guasch Maria, Minuzzi Luciele M, Misirkic Marjanovic Maja, Moellering Douglas R, Moisoi Nicoleta, Molina Anthony JA, Montaigne David, Moore Anthony L, Moore Christy, Moreau Kerrie, Moreira Bruno P, Moreno-Sanchez Rafael, Mracek Tomas, Muccini Anna Maria, Munro Daniel, Muntane Jordi, Muntean Danina M, Murray Andrew James, Musiol Eva, Nabben Miranda, Nair K Sreekumaran, Nehlin Jan O, Nemec Michal, Nesci Salvatore, Neufer P Darrell, Neuzil Jiri, Neviere Remi, Newsom Sean A, Norman Jennifer, Nozickova Katerina, Nunes Sara, Nuoffer Jean-Marc, O'Brien Kristin, O'Brien Katie A, O'Gorman Donal, Olgar Yusuf, Oliveira Ben, Oliveira Jorge, Oliveira Marcus F, Oliveira Marcos Tulio, Oliveira Pedro Fontes, Oliveira Paulo J, Olsen Rolf Erik, Orynbayeva Zulfiya, Osiewacz Heinz D, Paez Hector, Pak Youngmi Kim, Pallotta Maria Luigia, Palmeira Carlos, Parajuli Nirmala, Passos Joao F, Passrugger Manuela, Patel Hemal H, Pavlova Nadia, Pavlovic Kasja, Pecina Petr, Pedersen Tina M, Perales Jose Carles, Pereira da Silva Grilo da Silva Filomena, Pereira Rita, Pereira Susana P, Perez Valencia Juan Alberto, Perks Kara L, Pesta Dominik, Petit Patrice X, Pettersen Nitschke Ina Katrine, Pichaud Nicolas, Pichler Irene, Piel Sarah, Pietka Terri A, Pinho Sonia A, Pino Maria F, Pirkmajer Sergej, Place Nicolas, Plangger Mario, Porter Craig, Porter Richard K, Preguica Ines, Prigione Alessandro, Procaccio Vincent, Prochownik Edward V, Prola Alexandre, Pulinilkunnil Thomas, Puskarich Michael A, Puurand Marju, Radenkovic Filip, Ramzan Rabia, Rattan Suresh IS, Reano Simone, Reboredo-Rodriguez Patricia, Rees Bernard B, Renner-Sattler Kathrin, Rial Eduardo, Robinson Matthew M, Roden Michael, Rodrigues Ana Sofia, Rodriguez Enrique, Rodriguez-Enriquez Sara, Roesland Gro Vatne, Rohlena Jakub, Rolo Anabela Pinto, Ropelle Eduardo R, Roshanravan Baback, Rossignol Rodrigue, Rossiter Harry B, Rousar Tomas, Rubelj Ivica, Rybacka-Mossakowska Joanna, Saada Reisch Ann, Safaei Zahra, Salin Karine, Salvadego Desy, Sandi Carmen, Saner Nicholas, Santos Diana, Sanz Alberto, Sardao Vilma, Sarlak Saharnaz, Sazanov Leonid A, Scaife Paula, Scatena Roberto, Schartner Melanie, Scheibye-Knudsen Morten, Schilling Jan M, Schlattner Uwe, Schmitt Sabine, Schneider Gasser Edith Mariane, Schoenfeld Peter, Schots Pauke C, Schulz Rainer, Schwarzer Christoph, Scott Graham R, Selman Colin, Sendon Pamella Marie, Shabalina Irina G, Sharma Pushpa, Sharma Vipin, Shevchuk Igor, Shirazi Reza, Shiroma Jonathan G, Siewiera Karolina, Silber Ariel M, Silva Ana Maria, Sims Carrie A, Singer Dominique, Singh Brijesh Kumar, Skolik Robert A, Smenes Benedikte Therese, Smith James, Soares Felix Alexandre Antunes, Sobotka Ondrej, Sokolova Inna, Solesio Maria E, Soliz Jorge, Sommer Natascha, Sonkar Vijay K, Sova Marina, Sowton Alice P, Sparagna Genevieve C, Sparks Lauren M, Spinazzi Marco, Stankova Pavla, Starr Jonathan, Stary Creed, Stefan Eduard, Stelfa Gundega, Stepto Nigel K, Stevanovic Jelena, Stiban Johnny, Stier Antoine, Stocker Roland, Storder Julie, Sumbalova Zuzana, Suomalainen Anu, Suravajhala Prashanth, Svalbe Baiba, Swerdlow Russell H, Swiniuch Daria, Szabo Ildiko, Szewczyk Adam, Szibor Marten, Tanaka Masashi, Tandler Bernard, Tarnopolsky Mark A, Tausan Daniel, Tavernarakis Nektarios, Teodoro Joao Soeiro, Tepp Kersti, Thakkar Himani, Thapa Maheshwor, Thyfault John P, Tomar Dhanendra, Ton Riccardo, Torp May-Kristin, Torres-Quesada Omar, Towheed Atif, Treberg Jason R, Tretter Laszlo, Trewin Adam J, Trifunovic Aleksandra, Trivigno Catherine, Tronstad Karl Johan, Trougakos Ioannis P, Truu Laura, Tuncay Erkan, Turan Belma, Tyrrell Daniel J, Urban Tomas, Urner Sofia, Valentine Joseph Marco, Van Bergen Nicole J, Van der Ende Miranda, Varricchio Frederick, Vaupel Peter, Vella Joanna, Vendelin Marko, Vercesi Anibal E, Verdaguer Ignasi Bofill, Vernerova Andrea, Victor Victor Manuel, Vieira Ligo Teixeira Camila, Vidimce Josif, Viel Christian, Vieyra Adalberto, Vilks Karlis, Villena Josep A, Vincent Vinnyfred, Vinogradov Andrey D, Viscomi Carlo, Vitorino Rui Miguel Pinheiro, Vlachaki Walker Julia, Vogt Sebastian, Volani Chiara, Volska Kristine, Votion Dominique-Marie, Vujacic-Mirski Ksenija, Wagner Brett A, Ward Marie Louise, Warnsmann Verena, Wasserman David H, Watala Cezary, Wei Yau-Huei, Weinberger Klaus M, Weissig Volkmar, White Sarah Haverty, Whitfield Jamie, Wickert Anika, Wieckowski Mariusz R, Wiesner Rudolf J, Williams Caroline M, Winwood-Smith Hugh, Wohlgemuth Stephanie E, Wohlwend Martin, Wolff Jonci Nikolai, Wrutniak-Cabello Chantal, Wuest Rob CI, Yokota Takashi, Zablocki Krzysztof, Zanon Alessandra, Zanou Nadege, Zaugg Kathrin, Zaugg Michael, Zdrazilova Lucie, Zhang Yong, Zhang Yizhu, Zikova Alena, Zischka Hans, Zorzano Antonio, Zujovic Tijana, Zurmanova Jitka, Zvejniece Liga

Subjects
uncoupling, MitoPedia: Respiratory states, SI - The International System of Units, IUPAC, Coupling control, Mitochondrial preparations, Protonmotive force, Uncoupling, Oxidative phosphorylation, Phosphorylation efficiency, Electron transfer-pathway, LEAK-respiration, Residual oxygen consumption, Normalization of rate, Flow, Flux, Flux control ratio, Mitochondrial marker, Cell count, Oxygen, [SDV]Life Sciences [q-bio], coupling control, protonmotive force, oxidative phosphorylation, mitochondrial respiratory control, State 4, electron transfer, State 2, State 3, Mitochondrial physiology, residual oxygen consumption, flux, normalization, ion leak and slip compensatory state, efficiency, electron transfer system, flow, mitochondrial physiology, oxygen, mitochondrial preparations, proton leak
Abstract

As the knowledge base and importance of mitochondrial physiology to evolution, health and diseaseexpands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followthe latest SI guidelines and those of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute BEC 2020.1 doi:10.26124/bec:2020-0001.v1www.bioenergetics-communications.org3of 44to reproducibility between laboratories and thussupport the development of datarepositoriesof mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

Published
2020

7. Physical Activity and Mental Health of Patients with Pulmonary Hypertension during the COVID-19 Pandemic

Author

Dobler, Carolin Leoni, Krüger, Britta, Strahler, Jana, Weyh, Christopher, Gebhardt, Kristina, Tello, Khodr, Ghofrani, Hossein Ardeschir, Sommer, Natascha, Gall, Henning, Richter, Manuel Jonas, and Krüger, Karsten

Subjects
active lifestyle, lcsh:R, infection control measure, lcsh:Medicine, stress levels, resilience, Article, self-quarantine
Abstract

The aim of the study was to analyze the effect of personal restrictions on physical activity, mental health, stress experience, resilience, and sleep quality in patients with pulmonary hypertension (PH) during the &ldquo, lockdown&rdquo, period of the COVID-19 pandemic. In total, 112 PH patients and 52 age-matched healthy control subjects completed a questionnaire on the topics of physical activity, mental health, resilience, and sleep quality. PH patients had significantly lower physical activity, mental health, and sleep quality compared to age-matched healthy controls. Physical activity positively correlated with mental health and sleep quality in the PH group. Mental wellbeing and life satisfaction could be predicted by total physical activity, sleep, stress level, and resilience. PH patients appeared as an especially vulnerable group, demanding interventions to promote an active lifestyle and protect mental health in these patients. This could be helpful in counseling on how to carry out physical activity while maintaining infection control.

Published
2020

8. Blood Levels of Free-Circulating Mitochondrial DNA in Septic Shock and Postsurgical Systemic Inflammation and Its Influence on Coagulation: A Secondary Analysis of a Prospective Observational Study

Author

Schneck, Emmanuel, Edinger, Fabian, Hecker, Matthias, Sommer, Natascha, Pak, Oleg, Weissmann, Norbert, Hecker, Andreas, Reichert, Martin, Markmann, Melanie, Sander, Michael, and Koch, Christian

Subjects
sepsis, DAMPs, inflammation, lcsh:R, SIRS, lcsh:Medicine, coagulation, Article, coagulopathy
Abstract

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a potential biomarker for the discrimination between septic shock and postsurgical systemic inflammation. Overall, 80 patients were included (septic shock (n = 20), cardiac artery bypass grafting (CABG, n = 20), major abdominal surgery (MAS, n = 20), and matched controls (CTRL, n = 20)). Quantitative PCR was performed to measure ND1 mtDNA. Thromboelastography was used to analyze the coagulatory system. Free-circulating ND1 mtDNA levels were significantly higher in septic shock patients compared to patients suffering from post-surgical inflammation ({copies/&micro, L}: CTRL: 1208 (668&ndash, 2685), septic shock: 3823 (2170&ndash, 7318), CABG: 1272 (417&ndash, 2720), and MAS: 1356 (694&ndash, 2845), CTRL vs. septic shock: p &lt, 0.001, septic shock vs. CABG: p &lt, septic shock vs. MAS: p = 0.006, CABG vs. MAS: p = 0.01). ND1 mtDNA levels in CABG patients showed a strong positive correlation with fibrinogen (correlation coefficient [r]= 0.57, p &lt, 0.001) and fibrinogen-dependent thromboelastographic assays (maximum clot firmness, EXTEM: r = 0.35, p = 0.01, INTEM: r = 0.31, p = 0.02, FIBTEM: r = 0.46, p &lt, 0.001). In conclusion, plasma levels of free-circulating ND1 mtDNA were increased in septic shock patients and were discriminative between sepsis and surgery-induced inflammation. Furthermore, this study showed an association between ND1 mtDNA and a fibrinogen-dependent pro-coagulatory shift in cardiac surgical patients.

Published
2020

13. Doppler‐Derived Renal Venous Stasis Index in the Prognosis of Right Heart Failure

Author

Husain‐Syed, Faeq, Birk, Horst‐Walter, Ronco, Claudio, Schörmann, Tanja, Tello, Khodr, Richter, Manuel J., Wilhelm, Jochen, Sommer, Natascha, Steyerberg, Ewout, Bauer, Pascal, Walmrath, Hans‐Dieter, Seeger, Werner, McCullough, Peter A., Gall, Henning, and Ghofrani, H. Ardeschir

Subjects
Heart Failure, Aged, 80 and over, Male, Cardiorenal Syndrome, Hypertension, Pulmonary, intrarenal venous flow patterns, Ultrasonography, Doppler, venous congestion, Middle Aged, renal Doppler ultrasonography, Prognosis, Renal Veins, cardiorenal syndromes, pulmonary hypertension, Humans, Female, Prospective Studies, Vascular Diseases, Original Research, Aged
Abstract

Background Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods and Results We enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra‐abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH‐related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH‐specific therapy escalation) and all‐cause mortality for 1‐year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (P

Published
2019

15. Alternative Oxidase Attenuates Cigarette Smoke-induced Lung Dysfunction and Tissue Damage

Author

Giordano, Luca, Farnham, Antoine, Dhandapani, Praveen K., Salminen, Laura, Bhaskaran, Jahnavi, Voswinckel, Robert, Rauschkolb, Peter, Scheibe, Susan, Sommer, Natascha, Beisswenger, Christoph, Weissmann, Norbert, Braun, Thomas, Jacobs, Howard T., Bals, Robert, Herr, Christian, Szibor, Marten, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University

Subjects
Neutrophils, Chronic Obstructive Pulmonary Disease, Primary Cell Culture, Gene Expression, Apoptosis, Mice, Transgenic, Complex Mixtures, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, Cigarette Smoking, Mitochondrial Proteins, alternative oxidase, Mice, Pulmonary Disease, Chronic Obstructive, Cell Movement, Smoke, Tobacco, COPD, Animals, Lung, Original Research, Plant Proteins, cigarette smoke, Macrophages, Smoking, Sisätaudit - Internal medicine, Editorials, Fibroblasts, Embryo, Mammalian, Mitochondria, mitochondria, Disease Models, Animal, Oxidative Stress, Electron Transport Chain Complex Proteins, Female, Oxidoreductases, Reactive Oxygen Species, Signal Transduction
Abstract

Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain. AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months. It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS). In contrast, the early-phase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected. The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage, mitochondrial ROS production, and lung remodeling. Our findings implicate mitochondrial respiratory inhibition as a key pathogenic mechanism of CS toxicity in the lung. We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage.

Published
2018

16. Thin Air Resulting in High Pressure: Mountain Sickness and Hypoxia-Induced Pulmonary Hypertension

Author

Grimminger, Jan, Richter, Manuel, Tello, Khodr, Sommer, Natascha, Gall, Henning, and Ghofrani, Hossein Ardeschir

Subjects
Article Subject
Abstract

With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review summarizes current knowledge of the body’s acute response to these circumstances, possible complications and their treatment, and health care issues resulting from long-term exposure to high altitude. It furthermore describes the characteristic mechanisms of adaptation to life in hypobaric hypoxia expressed by the three major ethnic groups permanently dwelling at high altitude. We additionally summarize current knowledge regarding possible treatment options for hypoxia-induced pulmonary hypertension by reviewing in vitro, rodent, and human studies in this area of research.

Published
2017
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17. Additional file 1: Figure S1. of Survival with sildenafil and inhaled iloprost in a cohort with pulmonary hypertension: an observational study

Author

Gall, Henning, Sommer, Natascha, Milger, Katrin, Richter, Manuel, Voswinckel, Robert, Bandorski, Dirk, Seeger, Werner, Grimminger, Friedrich, and Hossein-Ardeschir Ghofrani

Subjects
cardiovascular system, lipids (amino acids, peptides, and proteins), respiratory system, musculoskeletal system, respiratory tract diseases
Abstract

Kaplanâ Meier plots of cumulative transplant-free survival in patients with pulmonary arterial hypertension associated with collagen-vascular disease, idiopathic pulmonary arterial hypertension, and pulmonary arterial hypertension associated with systemic-to-pulmonary shunt. Data are shown for patients who were treated with iloprost followed by addition of sildenafil (iloprost/sildenafil) or sildenafil followed by addition of iloprost (sildenafil/iloprost). (PDF 853Â kb)

Published
2016
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18. The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

Author

Richter, Manuel Jonas, Milger, Katrin, Haase, Sarah, Sommer, Natascha, Tello, Khodr, Seeger, Werner, Mayer, Eckhard, Wiedenroth, Christoph Benjamin, Grimminger, Friedrich, George, Wolfgang, Ghofrani, Hossein Ardeschir, Guth, Stefan, Gall, Henning, and Justus Liebig University Giessen

Subjects
ddc:610
Abstract

Background: Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH. Methods: Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA. Results: 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH. Conclusions: This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA.

Published
2016
Full Text
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19. Additional file 1: Figure S1. of Survival with sildenafil and inhaled iloprost in a cohort with pulmonary hypertension: an observational study

Author

Gall, Henning, Sommer, Natascha, Milger, Katrin, Richter, Manuel, Voswinckel, Robert, Bandorski, Dirk, Seeger, Werner, Grimminger, Friedrich, and Hossein-Ardeschir Ghofrani

Subjects
cardiovascular system, lipids (amino acids, peptides, and proteins), respiratory system, musculoskeletal system, respiratory tract diseases
Abstract

Kaplanâ Meier plots of cumulative transplant-free survival in patients with pulmonary arterial hypertension associated with collagen-vascular disease, idiopathic pulmonary arterial hypertension, and pulmonary arterial hypertension associated with systemic-to-pulmonary shunt. Data are shown for patients who were treated with iloprost followed by addition of sildenafil (iloprost/sildenafil) or sildenafil followed by addition of iloprost (sildenafil/iloprost). (PDF 853Â kb)

Published
2016
Full Text
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20. The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

Author

Richter, Manuel Jonas, Milger, Katrin, Haase, Sarah, Sommer, Natascha, Tello, Khodr, Seeger, Werner, Mayer, Eckhard, Wiedenroth, Christoph Benjamin, Grimminger, Friedrich, George, Wolfgang, Ghofrani, Hossein Ardeschir, Guth, Stefan, Gall, Henning, and Department of Internal Medicine

Subjects
Male, Pulmonology, lcsh:Medicine, Biochemistry, Cohort Studies, Endocrinology, Glucose Metabolism, Natriuretic Peptide, Brain, Diabetes diagnosis and management, Prospective Studies, Pulmonary Arteries, lcsh:Science, Immunoassay, Pulmonary Hypertension, Hematology, Arteries, Middle Aged, Plants, Prognosis, Legumes, Creatinine, Carbohydrate Metabolism, Female, Anatomy, Research Article, HbA1c, Endocrine Disorders, Hypertension, Pulmonary, Endarterectomy, Pulmonary Artery, Diabetes Mellitus, Humans, Arterial Pressure, ddc:610, Hemoglobin, Aged, Glycated Hemoglobin, Medicine and health sciences, Biology and life sciences, lcsh:R, Hemodynamics, Organisms, Peas, Proteins, Medical sciences Medicine, Peptide Fragments, Diagnostic medicine, Logistic Models, Metabolism, Metabolic Disorders, Chronic Disease, Cardiovascular Anatomy, Blood Vessels, lcsh:Q, Biomarkers
Abstract

Background: Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH. Methods: Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA. Results: 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH. Conclusions: This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA.

Published
2016

21. Mitochondria and cellular cytochromes as oxygen sensors in hypoxic pulmonary vasoconstriction

Author

Sommer, Natascha and Zentrum für Innere Medizin, Medizinische Klinik II

Subjects
Hypoxie, mitochondria, oxygen sensor, cytochromes, hypoxia, Lunge, ddc:610, Mitochondrien, Zytochrome, Medical sciences Medicine, Sauerstoffsensor, lung
Abstract

Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung to match blood perfusion to alveolar ventilation and optimize pulmonary gas exchange. Mitochondria have been suggested as possible O2 sensors of HPV. With regard to mitochondria the hypothesis of an increased or decreased production of reactive oxygen species (ROS) at complex I or III competes with the hypothesis of a localized small decrease of ATP production. Against this background, the present study investigated the O2 dependent regulation of mitochondrial cytochrome redox state and respiration in isolated lungs and pulmonary arterial smooth muscle cells (PASMC). Methodological limitations of the past were overcome by detection of mitochondrial cytochrome redox state under hypoxic and normoxic conditions using remission spectrophotometry in intact lungs and in PASMC. High-resolution respirometry was used to determine the respiration simultaneously in isolated cells. These alterations were compared to HPV and hypoxia-induced cellular responses, such as mitochondrial matrix superoxide release and mitochondrial membrane potential. Aortic and renal arterial smooth muscle cells (ASMC, RASMC) served as controls. The hypoxia-induced decrease of mitochondrial respiration paralleled the increase in the strength of HPV in isolated lungs. In PASMC, reduction of respiration and mitochondrial cytochrome c and aa3 (complex IV) matched an increase in matrix superoxide levels, as well as mitochondrial membrane hyperpolarization. Cytochrome bl/h (complex III) was relatively more oxidized during hypoxia compared to cytochrome c and aa3. In contrast to PASMC, RASMC displayed a smaller decrease in respiration and no rise in superoxide or mitochondrial membrane potential. Pharmacological inhibition of mitochondria revealed analogous kinetics of cytochrome redox state and the strength of HPV. The data of this thesis thus suggest inhibition of complex IV as an essential step in mitochondrial O2 sensing of HPV. Concomitantly, increased superoxide release from complex III and mitochondrial membrane hyperpolarization may initiate the pathway underlying HPV. In isolated lungs, HPV may be modulated by oxygenation state of hemoglobin, whereas there is no evidence for carbon monoxide playing a role via cytochrome P450. Die hypoxische pulmonale Vasokonstriktion (HPV) ist ein wesentlicher Mechanismus der Lunge, um die Perfusion an die alveoläre Ventilation anzupassen und so den pulmonalen Gasaustausch zu optimieren. Mitochondrien sind dabei möglicherweise die Sauerstoffsensoren der HPV. Derzeit bestehen konkurrierende Hypothesen bezüglich eines mitochondrialen Sensing-Mechanismus: Eine erhöhte oder erniedrige Produktion von Sauerstoffradikalen am Komplex I oder III oder eine lokalisierte, leichte Abnahme der ATP Produktion könnten die Signalkaskade einleiten. Vor diesem Hintergrund, untersuchte die vorliegenden Arbeit die sauerstoffabhängige Regulation des Redox-Status’ mitochondrialer Cytochrome und der mitochondrialen Atmung in der isoliert perfundierten und ventilierten Lunge und in glatten Muskelzellen pulmonalarterieller Gefäße (PASMC). Methodische Limitationen bisheriger Untersuchungen wurden durch die Anwendung von Remissionspektrometrie überwunden, wodurch der Redox-Status mitochondrialer Cytochrome während Hypoxie und Normoxie in intakten Lungen und PASMC bestimmt werden konnte. Mit hochauflösender Respirometrie wurde gleichzeitig die Atmung in isolierten Zellen erfasst. Veränderungen dieser Parameter wurden mit der Stärke der HPV und Hypoxie-induzierten zellulären Antworten in isolierten Zellen, wie Superoxidfreisetzung in der mitochondrialen Matrix und dem mitochondrialen Membranpotential, verglichen. Zur Kontrolle wurden glatte Gefässmuskelzellen der Aorta und der Nierenarterie (ASMC, RASMC) herangezogen. Eine hypoxie-induzierte Abnahme der mitochondrialen Atmung erfolgte gleichzeitig mit Beginn der HPV in der isolierten Lunge. In isolierten PASMC ging die Abnahme der Atmung und Reduktion der mitochondrialen Cytochrome c und aa3 (Komplex IV) mit einem Anstieg der Superoxidkonzentration in der mitochondrialen Matrix, sowie einer mitochondrialen Membranhyperpolarisierung einher. Cytochom bl/h (Komplex III) war bezogen auf Cytochrom c und aa3 unter Hypoxie mehr oxidiert. Im Gegensatz zu PASMC, zeigten RASMC eine niedrigere Abnahme der Atmung und keinen Anstieg von Superoxid oder dem Membranpotential unter Hypoxie. Während pharmakologischer Inhibierung der Mitochondrien korrespondierte der cytochromale Redox-Status mit der Stärke der HPV. Die Daten der vorliegenden Arbeit legen daher nahe, dass die Inhibierung von Komplex IV ein wesentlicher Schritt beim mitochondrialen Sauerstoffsensing der HPV ist. Gleichzeitig könnte ein Anstieg der Sauerstoffradikalfreisetzung von Komplex III und des mitochondrialen Membranpotentials die der HPV zugrunde liegende Signaltransduktion initiieren. In isolierten Lungen ist die HPV ausserdem möglicherweise durch den Oxygenierungstatus des Hemoglobin moduliert, während es keinen Hinweis darauf gibt, dass Kohlenmonoxid mittels Cytochrome P450 Interaktion eine Rolle spielt.

Published
2011

22. Mitochondria and cellular cytochromes as oxygen sensors in hypoxic pulmonary vasoconstriction

Author

Sommer, Natascha and Justus Liebig University Giessen

Subjects
Hypoxie, mitochondria, oxygen sensor, cytochromes, ddc:610, hypoxia, Lunge, Mitochondrien, Zytochrome, Sauerstoffsensor, lung
Abstract

Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung to match blood perfusion to alveolar ventilation and optimize pulmonary gas exchange. Mitochondria have been suggested as possible O2 sensors of HPV. With regard to mitochondria the hypothesis of an increased or decreased production of reactive oxygen species (ROS) at complex I or III competes with the hypothesis of a localized small decrease of ATP production. Against this background, the present study investigated the O2 dependent regulation of mitochondrial cytochrome redox state and respiration in isolated lungs and pulmonary arterial smooth muscle cells (PASMC).Methodological limitations of the past were overcome by detection of mitochondrial cytochrome redox state under hypoxic and normoxic conditions using remission spectrophotometry in intact lungs and in PASMC. High-resolution respirometry was used to determine the respiration simultaneously in isolated cells. These alterations were compared to HPV and hypoxia-induced cellular responses, such as mitochondrial matrix superoxide release and mitochondrial membrane potential. Aortic and renal arterial smooth muscle cells (ASMC, RASMC) served as controls. The hypoxia-induced decrease of mitochondrial respiration paralleled the increase in the strength of HPV in isolated lungs. In PASMC, reduction of respiration and mitochondrial cytochrome c and aa3 (complex IV) matched an increase in matrix superoxide levels, as well as mitochondrial membrane hyperpolarization. Cytochrome bl/h (complex III) was relatively more oxidized during hypoxia compared to cytochrome c and aa3. In contrast to PASMC, RASMC displayed a smaller decrease in respiration and no rise in superoxide or mitochondrial membrane potential. Pharmacological inhibition of mitochondria revealed analogous kinetics of cytochrome redox state and the strength of HPV.The data of this thesis thus suggest inhibition of complex IV as an essential step in mitochondrial O2 sensing of HPV. Concomitantly, increased superoxide release from complex III and mitochondrial membrane hyperpolarization may initiate the pathway underlying HPV.In isolated lungs, HPV may be modulated by oxygenation state of hemoglobin, whereas there is no evidence for carbon monoxide playing a role via cytochrome P450., Die hypoxische pulmonale Vasokonstriktion (HPV) ist ein wesentlicher Mechanismus der Lunge, um die Perfusion an die alveoläre Ventilation anzupassen und so den pulmonalen Gasaustausch zu optimieren. Mitochondrien sind dabei möglicherweise die Sauerstoffsensoren der HPV. Derzeit bestehen konkurrierende Hypothesen bezüglich eines mitochondrialen Sensing-Mechanismus: Eine erhöhte oder erniedrige Produktion von Sauerstoffradikalen am Komplex I oder III oder eine lokalisierte, leichte Abnahme der ATP Produktion könnten die Signalkaskade einleiten. Vor diesem Hintergrund, untersuchte die vorliegenden Arbeit die sauerstoffabhängige Regulation des Redox-Status mitochondrialer Cytochrome und der mitochondrialen Atmung in der isoliert perfundierten und ventilierten Lunge und in glatten Muskelzellen pulmonalarterieller Gefäße (PASMC).Methodische Limitationen bisheriger Untersuchungen wurden durch die Anwendung von Remissionspektrometrie überwunden, wodurch der Redox-Status mitochondrialer Cytochrome während Hypoxie und Normoxie in intakten Lungen und PASMC bestimmt werden konnte. Mit hochauflösender Respirometrie wurde gleichzeitig die Atmung in isolierten Zellen erfasst. Veränderungen dieser Parameter wurden mit der Stärke der HPV und Hypoxie-induzierten zellulären Antworten in isolierten Zellen, wie Superoxidfreisetzung in der mitochondrialen Matrix und dem mitochondrialen Membranpotential, verglichen. Zur Kontrolle wurden glatte Gefässmuskelzellen der Aorta und der Nierenarterie (ASMC, RASMC) herangezogen. Eine hypoxie-induzierte Abnahme der mitochondrialen Atmung erfolgte gleichzeitig mit Beginn der HPV in der isolierten Lunge. In isolierten PASMC ging die Abnahme der Atmung und Reduktion der mitochondrialen Cytochrome c und aa3 (Komplex IV) mit einem Anstieg der Superoxidkonzentration in der mitochondrialen Matrix, sowie einer mitochondrialen Membranhyperpolarisierung einher. Cytochom bl/h (Komplex III) war bezogen auf Cytochrom c und aa3 unter Hypoxie mehr oxidiert. Im Gegensatz zu PASMC, zeigten RASMC eine niedrigere Abnahme der Atmung und keinen Anstieg von Superoxid oder dem Membranpotential unter Hypoxie. Während pharmakologischer Inhibierung der Mitochondrien korrespondierte der cytochromale Redox-Status mit der Stärke der HPV.Die Daten der vorliegenden Arbeit legen daher nahe, dass die Inhibierung von Komplex IV ein wesentlicher Schritt beim mitochondrialen Sauerstoffsensing der HPV ist. Gleichzeitig könnte ein Anstieg der Sauerstoffradikalfreisetzung von Komplex III und des mitochondrialen Membranpotentials die der HPV zugrunde liegende Signaltransduktion initiieren. In isolierten Lungen ist die HPV ausserdem möglicherweise durch den Oxygenierungstatus des Hemoglobin moduliert, während es keinen Hinweis darauf gibt, dass Kohlenmonoxid mittels Cytochrome P450 Interaktion eine Rolle spielt.

Published
2011
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