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3. LegoNet: Alternating Model Blocks for Medical Image Segmentation

Author

Sobirov, Ikboljon, Xie, Cheng, Siddique, Muhammad, Patel, Parijat, Chan, Kenneth, Halborg, Thomas, Kotanidis, Christos, Fatima, Zarqiash, West, Henry, Channon, Keith, Neubauer, Stefan, Antoniades, Charalambos, and Yaqub, Mohammad

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Since the emergence of convolutional neural networks (CNNs), and later vision transformers (ViTs), the common paradigm for model development has always been using a set of identical block types with varying parameters/hyper-parameters. To leverage the benefits of different architectural designs (e.g. CNNs and ViTs), we propose to alternate structurally different types of blocks to generate a new architecture, mimicking how Lego blocks can be assembled together. Using two CNN-based and one SwinViT-based blocks, we investigate three variations to the so-called LegoNet that applies the new concept of block alternation for the segmentation task in medical imaging. We also study a new clinical problem which has not been investigated before, namely the right internal mammary artery (RIMA) and perivascular space segmentation from computed tomography angiography (CTA) which has demonstrated a prognostic value to major cardiovascular outcomes. We compare the model performance against popular CNN and ViT architectures using two large datasets (e.g. achieving 0.749 dice similarity coefficient (DSC) on the larger dataset). We evaluate the performance of the model on three external testing cohorts as well, where an expert clinician made corrections to the model segmented results (DSC>0.90 for the three cohorts). To assess our proposed model for suitability in clinical use, we perform intra- and inter-observer variability analysis. Finally, we investigate a joint self-supervised learning approach to assess its impact on model performance. The code and the pretrained model weights will be available upon acceptance., Comment: 12 pages, 5 figures, 4 tables

Published
2023

4. Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data

Author

Soltani, Fardad, Jenkins, David A., Kaura, Amit, Bradley, Joshua, Black, Nicholas, Farrant, John P., Williams, Simon G., Mulla, Abdulrahim, Glampson, Benjamin, Davies, Jim, Papadimitriou, Dimitri, Woods, Kerrie, Shah, Anoop D., Thursz, Mark R., Williams, Bryan, Asselbergs, Folkert W., Mayer, Erik K., Herbert, Christopher, Grant, Stuart, Curzen, Nick, Squire, Iain, Johnson, Thomas, O’Gallagher, Kevin, Shah, Ajay M., Perera, Divaka, Kharbanda, Rajesh, Patel, Riyaz S., Channon, Keith M., Lee, Richard, Peek, Niels, Mayet, Jamil, and Miller, Christopher A.

Published
2024
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5. Prognostic significance of troponin in patients with malignancy (NIHR Health Informatics Collaborative TROP-MALIGNANCY study)

Author

Samuel, Nathan A., Roddick, Alistair, Glampson, Ben, Mulla, Abdulrahim, Davies, Jim, Papadimitriou, Dimitri, Panoulas, Vasileios, Mayer, Erik, Woods, Kerrie, Shah, Anoop D., Gautama, Sanjay, Elliott, Paul, Hemmingway, Harry, Williams, Bryan, Asselbergs, Folkert W., Melikian, Narbeh, Kharbanda, Rajesh, Shah, Ajay M., Perera, Divaka, Patel, Riyaz S., Channon, Keith M., Mayet, Jamil, Shah, Anoop S. V., and Kaura, Amit

Published
2024
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7. Clinical Significance of Myocardial Injury in Patients Hospitalized for COVID-19: A Prospective, Multicenter, Cohort Study

Author

Greenwood, J.P., McCann, G.P., Berry, C., Dweck, M., Miller, C.M., Chiribiri, A., Prasad, S., Ferreira, V.M., Bucciarelli-Ducci, C., Dawson, D., Moon, James C., Artico, Jessica, Shiwani, Hunain, Davies, Rhodri, Dweck, Marc, Berry, Colin, Roditi, Giles, Young, Robin, McConnachie, Alex, Kelly, Bernard, Macfarlane, Peter W., Miller, Christopher A., Levelt, Eylem, Goreka, Miroslawa, Somers, Kathryn, Byrom-Goulthorp, Roo J., Anderson, Michelle, Britton, Laura, Richards, Fiona, Jones, Laura M., Arnold, Ranjit, Moss, Alastair, Fisher, Jude, Wormleighton, Joanne, Parke, Kelly, Wright, Rachel, Yeo, Jian, Dawson, Dana, Falconer, Judith, Harries, Valerie, Henderson, Paula, Singh, Trisha, Newby, David, Piechnik, Stefan, Popescu, Iulia, Lukaschuk, Elena, Zhang, Qiang, Shanmuganathan, Mayooran, Neubauer, Stefan, Raman, Betty, Channon, Keith, Krasopoulos, Catherine, Nunes, Claudia, Da Silva Rodrigues, Liliana, Nixon, Harriet, Panopoulou, Athanasia, Fletcher, Alison, Manley, Peter, Mangion, Kenneth, Morrow, Andrew, Sykes, Robert, Fallon, Kirsty, Brown, Ammani, Kelly, Laura, McGinley, Christopher, Briscoe, Michael, Woodward, Rosemary, Hopkins, Tracey, McLennan, Evonne, Tynan, Nicola, Dymock, Laura, Swoboda, Peter, Wright, Judith, Exley, Donna, Steeds, Richard, Hutton, Kady, MacDonald, Sonia, Treibel, Thomas, Shetye, Abhishek, Miller, Christopher M., Orsborne, Christopher, Woodville-Jones, William, Ferguson, Susan, Bratis, Konstantinos, Fairbairn, Timothy, Sionas, Michail, Widdows, Peris, Chew, Pei Gee, Marsden, Christian, Collins, Tom, George, Linsha, Kearney, Lisa, Flett, Andrew, Smith, Simon, Zhenge, Alice, Harvey, Jake, Inacio, Liliana, Hanam-Penfold, Tomas, Gruner, Lucy, Fontana, Marianna, Razvi, Yousuf S.K., Crause, Jacolene, Davies, Nina M., Brown, James T., Chaco, Liza, Patel, Rishi, Kotecha, Tushar, Knight, Dan S., Green, Thomas, Ripley, David, Thompson, Maria, Chiribiri, Amedeo, Akerele, Ugochi, Cifra, Elna, Alskaf, Ebraham, Crawley, Richard, Villa, Adriana, Bucciarelli-Ducci, Chiara, Nightingale, Angus K., Wright, Kim, Bonnick, Esther D., Hopkins, Emma, George, Jessy, Joseph, Linta, Cole, Graham, Vimalesvaran, Kavitha, Ali, Nadine, Carr, Caitlin R., Ross, Alexandra A.R., King, Clara, Prasad, Sanjay, Farzad, Zohreh, Salmi, Sara A., Kirby, Kevin, McDiarmid, Adam, Stevenson, Hannah J., Matsvimbo, Pamela S., Joji, Lency, Fearby, Margaret, Brown, Benjamin, Bunce, Nicholas, Jennings, Robert, Sookhoo, Vennessa, Joshi, Shatabdi, Kanagala, Prathap, Fullalove, Sandra, Toohey, Catherine, Fenlon, Kate, Bellenger, Nicholas, He, Jingzhou, Statton, Sarah, Pamphilon, Nicola, Steele, Anna, Ball, Claire, McGahey, Ann, Balma, Silvia, Wilkes, Lynsey, Lewis, Katy, Walter, Michelle, Ionescu, Adrian, Ninan, Tishi, Richards, Suzanne, Williams, Marie, Alfakih, Khaled, Pilgrim, Samia, Joy, George, Manisty, Charlotte H., Hussain, Ifza, Gorecka, Miroslawa, McCann, Gerry P., Alzahir, Mohammed, Ramirez, Sara, Lin, Andrew, Swoboda, Peter P., McDiarmid, Adam K., Manisty, Charlotte, Treibel, Thomas A., Piechnik, Stefan K., Davies, Rhodri H., Ferreira, Vanessa M., Dweck, Marc R., and Greenwood, John P.

Published
2024
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9. Cardiovascular Magnetic Resonance Before Invasive Coronary Angiography in Suspected Non–ST-Segment Elevation Myocardial Infarction

Author

Shanmuganathan, Mayooran, Nikolaidou, Chrysovalantou, Burrage, Matthew K., Borlotti, Alessandra, Kotronias, Rafail, Scarsini, Roberto, Banerjee, Abhirup, Terentes-Printzios, Dimitrios, Pitcher, Alex, Gara, Edit, Langrish, Jeremy, Lucking, Andrew, Choudhury, Robin, De Maria, Giovanni Luigi, Banning, Adrian, Piechnik, Stefan K., Channon, Keith M., and Ferreira, Vanessa M.

Published
2024
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10. Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group

Author

Mézquita, Aldo J. Vázquez, Biavati, Federico, Falk, Volkmar, Alkadhi, Hatem, Hajhosseiny, Reza, Maurovich-Horvat, Pál, Manka, Robert, Kozerke, Sebastian, Stuber, Matthias, Derlin, Thorsten, Channon, Keith M., Išgum, Ivana, Coenen, Adriaan, Foellmer, Bernhard, Dey, Damini, Volleberg, Rick H. J. A., Meinel, Felix G., Dweck, Marc R., Piek, Jan J., van de Hoef, Tim, Landmesser, Ulf, Guagliumi, Giulio, Giannopoulos, Andreas A., Botnar, René M., Khamis, Ramzi, Williams, Michelle C., Newby, David E., and Dewey, Marc

Published
2023
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11. Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study

Author

Thomas, Sheena, Denton, Jon, Farral, Robyn, Taylor, Carolyn, Qin, Wendy, Kasongo, Mary, Anthony, Susan, Banning, Adrian, Xie, Cheng, Kharbanda, Rajesh K, Pritchard, Amy, Halborg, Thomas, Syed, Nigar, Fry, Sam, Mathers, Chris, Rose, Anne, Hudson, George, Bajaj, Amrita, Das, Intrajeet, Deshpande, Aparna, Rao, Praveen, Lawday, Dan, Mirsadraee, Saeed, Hudson, Benjamin, Berry, Colin, Marwan, Mohamed, Maurovich-Horvat, Pál, He, Guo-Wei, Lin, Wen-Hua, Fan, Li-Juan, Takahashi, Naohiko, Kondo, Hidekazu, Dai, Neng, Ge, Junbo, Koo, Bon-Kwon, Guglielmo, Marco, Pontone, Gianluca, Huck, Daniel, Benedek, Theodora, Rajani, Ronak, Vilic, Dijana, Aljazzaf, Haleema, Mun, Mak S, Benedetti, Giulia, Preston, Rebecca L, Raisi-Estabragh, Zahra, Connolly, Derek L, Sharma, Vinoda, Grenfell, Rebecca, Bradlow, William, Schmitt, Matthias, Serfaty, Fabiano, Gottlieb, Ilan, Neves, Mario FT, Newby, David E, Dweck, Marc R, Hatem, Stéphane, Redheuil, Alban, Benetos, Georgios, Beer, Meinrad, Granillo, Gastón AR, Selvanayagam, Joseph, Lopez-Jimenez, Francisco, De Bosscher, Ruben, Tavildari, Alain, Figtree, Gemma, Danad, Ibrahim, Shantouf, Ronney, Kietselaer, Bas, Tousoulis, Dimitris, Dangas, George, Mehta, Nehal N, Kontanidis, Christos, Kunadian, Vijay, Fairbairn, Timothy A, Chan, Kenneth, Wahome, Elizabeth, Tsiachristas, Apostolos, Antonopoulos, Alexios S, Patel, Parijat, Lyasheva, Maria, Kingham, Lucy, West, Henry, Oikonomou, Evangelos K, Volpe, Lucrezia, Mavrogiannis, Michail C, Nicol, Edward, Mittal, Tarun K, Kotronias, Rafail A, Adlam, David, Modi, Bhavik, Rodrigues, Jonathan, Screaton, Nicholas, Kardos, Attila, Greenwood, John P, Sabharwal, Nikant, De Maria, Giovanni Luigi, Munir, Shahzad, McAlindon, Elisa, Sohan, Yogesh, Tomlins, Pete, Siddique, Muhammad, Kelion, Andrew, Shirodaria, Cheerag, Pugliese, Francesca, Petersen, Steffen E, Blankstein, Ron, Desai, Milind, Gersh, Bernard J, Achenbach, Stephan, Libby, Peter, Neubauer, Stefan, Channon, Keith M, Deanfield, John, and Antoniades, Charalambos

Published
2024
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13. Comparison of bolus versus continuous thermodilution derived indices of microvascular dysfunction in revascularized coronary syndromes

Author

Fawaz, Samer, Marin, Federico, Khan, Sarosh A, F G Simpson, Rupert, Kotronias, Rafail A, Chai, Jason, Acute Myocardial Infarction (OxAMI) Study Investigators, Oxford, Al-Janabi, Firas, Jagathesan, Rohan, Konstantinou, Klio, Mohdnazri, Shah R, Clesham, Gerald J, Tang, Kare H, Cook, Christopher M, Channon, Keith M, Banning, Adrian P, Davies, John R, V Karamasis, Grigoris, De Maria, Giovanni L, and Keeble, Thomas R

Published
2024
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14. Angiography-Derived Index of Microcirculatory Resistance to Define the Risk of Early Discharge in STEMI

Author

Scarsini, Roberto, Kotronias, Rafail A., Della Mora, Francesco, Portolan, Leonardo, Andreaggi, Stefano, Benenati, Stefano, Marin, Federico, Sgreva, Sara, Comuzzi, Alberto, Butturini, Caterina, Pesarini, Gabriele, Tavella, Domenico, Channon, Keith M., Garcia Garcia, Hector M., Ribichini, Flavio, Banning, Adrian P., and De Maria, Giovanni Luigi

Published
2024
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16. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Ahern, David J, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, Lin, Wen-Hua, Kotanidis, Christos P, Rodrigues, Jonathan C L, O’Connor, Daniel, Siddique, Muhammad, Lockstone, Helen, Oikonomou, Evangelos K, Badi, Ileana, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Indrajeet, Das, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Newby, David E, Channon, Keith M, and Antoniades, Charalambos

Published
2022
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17. Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review

Author

Ademi, Zanfina, Avis, Suzanne Robyn, Chan, Adam, Contreras, Osvaldo, Coorey, Craig P., Fathieh, Sina, Genetzakis, Elijah, Gholipour, Alireza, Giles, Corey, Hollings, Matthew, Hyun, Karice, Kazi, Samia, Kovacic, Jason C., Larance, Mark, Marathe, Jessica A., Marquina, Clara, Nelson, Adam, Ng, Hooi Hooi, Patrick, Ellis, Peter, Karlheinz, Tran, Andy, Yang, Jean, Zhu, Dantong, Zwack, Clara, Figtree, Gemma A., Vernon, Stephen T., Harmer, Jason A., Gray, Michael P., Arnott, Clare, Bachour, Eric, Barsha, Giannie, Brieger, David, Brown, Alex, Celermajer, David S., Channon, Keith M., Chew, Nicholas W.S., Chong, James J.H., Chow, Clara K., Cistulli, Peter A., Ellinor, Patrick T., Grieve, Stuart M., Guzik, Tomasz J., Hagström, Emil, Jenkins, Alicia, Jennings, Garry, Keech, Anthony C., Kott, Katharine A., Kritharides, Leonard, Mamas, Mamas A., Mehran, Roxana, Meikle, Peter J., Natarajan, Pradeep, Negishi, Kazuaki, O’Sullivan, John, Patel, Sanjay, Psaltis, Peter J., Redfern, Julie, Steg, Philippe G., Sullivan, David R., Sundström, Johan, Vogel, Birgit, Wilson, Andrew, Wong, Dennis, Bhatt, Deepak L., and Nicholls, Stephen J.

Published
2023
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18. Role of Human Epicardial Adipose Tissue–Derived miR-92a-3p in Myocardial Redox State

Author

Carena, Maria Cristina, Badi, Ileana, Polkinghorne, Murray, Akoumianakis, Ioannis, Psarros, Costas, Wahome, Elizabeth, Kotanidis, Christos P., Akawi, Nadia, Antonopoulos, Alexios S., Chauhan, Jagat, Sayeed, Rana, Krasopoulos, George, Srivastava, Vivek, Farid, Shakil, Walcot, Nicholas, Douglas, Gillian, Channon, Keith M., Casadei, Barbara, and Antoniades, Charalambos

Published
2023
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19. Deep-Learning for Epicardial Adipose Tissue Assessment With Computed Tomography: Implications for Cardiovascular Risk Prediction

Author

West, Henry W., Siddique, Muhammad, Williams, Michelle C., Volpe, Lucrezia, Desai, Ria, Lyasheva, Maria, Thomas, Sheena, Dangas, Katerina, Kotanidis, Christos P., Tomlins, Pete, Mahon, Ciara, Kardos, Attila, Adlam, David, Graby, John, Rodrigues, Jonathan C.L., Shirodaria, Cheerag, Deanfield, John, Mehta, Nehal N., Neubauer, Stefan, Channon, Keith M., Desai, Milind Y., Nicol, Edward D., Newby, David E., and Antoniades, Charalambos

Published
2023
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21. The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade

Author

Kalla, Manish, Hao, Guoliang, Tapoulal, Nidi, Tomek, Jakub, Liu, Kun, Woodward, Lavinia, Dall’Armellina, Erica, Banning, Adrian P, Choudhury, Robin P, Neubauer, Stefan, Kharbanda, Rajesh K, Channon, Keith M, Ajijola, Olujimi A, Shivkumar, Kalyanam, Paterson, David J, and Herring, Neil

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Heart Disease, Neurosciences, Heart Disease - Coronary Heart Disease, Cardiovascular, Prevention, Animals, Heart, Humans, Neuropeptide Y, Percutaneous Coronary Intervention, Rats, ST Elevation Myocardial Infarction, Ventricular Fibrillation, Myocardial infarction, Percutaneous coronary intervention, Ventricular tachycardia, Ventricular fibrillation, ‘Oxford Acute Myocardial Infarction (OxAMI) Study’, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

AimsST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors.Methods and resultsIn 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P

Published
2020

23. Abstract 15072: Lipoprotein(a) Regulates Vascular Redox State and Predicts Adverse Cardiovascular Outcomes in Coronary Artery Disease

Author

Polkinghorne, Murray D, Xie, Cheng, CHAUHAN, JAGAT SINGH, Baragetti, Andrea, Patel, Parijat, de Araujo, Edmarcia, Wahome, Elizabeth, Kotanidis, Christos, Akoumianakis, Ioannis, Krasopoulos, George, Walcot, Nicholas, Badi, Ileana, Channon, Keith M, Guzik, Tomasz J, Norata, Giuseppe Danilo D, and Antoniades, Charalambos

Published
2023
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24. Acute Response in the Noninfarcted Myocardium Predicts Long-Term Major Adverse Cardiac Events After STEMI

Author

Shanmuganathan, Mayooran, Masi, Ambra, Burrage, Matthew K., Kotronias, Rafail A., Borlotti, Alessandra, Scarsini, Roberto, Banerjee, Abhirup, Terentes-Printzios, Dimitrios, Zhang, Qiang, Hann, Evan, Tunnicliffe, Elizabeth, Lucking, Andrew, Langrish, Jeremy, Kharbanda, Rajesh, De Maria, Giovanni Luigi, Banning, Adrian P., Choudhury, Robin P., Channon, Keith M., Piechnik, Stefan K., and Ferreira, Vanessa M.

Published
2023
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25. Clinical Utility of Cardiovascular Magnetic Resonance Before Invasive Coronary Angiography in Suspected Non-ST-segment-Elevation Myocardial Infarction

Author

Shanmuganathan, Mayooran, primary, Nikolaidou, Chrysovalantou, additional, Burrage, Matthew K., additional, Borlotti, Alessandra, additional, Kotronias, Rafail, additional, Scarsini, Roberto, additional, Banerjee, Abhirup, additional, Terentes-Printzios, Dimitrios, additional, Pitcher, Alex, additional, Gara, Edit, additional, Langrish, Jeremy, additional, Lucking, Andrew, additional, Choudhury, Robin, additional, De Maria, Giovanni Luigi, additional, Banning, Adrian, additional, Piechnik, Stefan K., additional, Channon, Keith M., additional, and Ferreira, Vanessa M., additional

Published
2024
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26. Neutrophils incite and macrophages avert electrical storm after myocardial infarction

Author

Grune, Jana, Lewis, Andrew J. M., Yamazoe, Masahiro, Hulsmans, Maarten, Rohde, David, Xiao, Ling, Zhang, Shuang, Ott, Christiane, Calcagno, David M., Zhou, Yirong, Timm, Kerstin, Shanmuganathan, Mayooran, Pulous, Fadi E., Schloss, Maximillian J., Foy, Brody H., Capen, Diane, Vinegoni, Claudio, Wojtkiewicz, Gregory R., Iwamoto, Yoshiko, Grune, Tilman, Brown, Dennis, Higgins, John, Ferreira, Vanessa M., Herring, Neil, Channon, Keith M., Neubauer, Stefan, Sosnovik, David E., Milan, David J., Swirski, Filip K., King, Kevin R., Aguirre, Aaron D., Ellinor, Patrick T., and Nahrendorf, Matthias

Published
2022
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27. External stenting and disease progression in saphenous vein grafts two years after coronary artery bypass grafting: A multicenter randomized trial

Author

Benedetto, Umberto, Vohra, Hunaid, Bittar, Mohamad Nidal, Bose, Amal, Berman, Marius, Kharbanda, Rajesh, Paraforos, Alexandros, Ladyshenskij, Leonid, Bonaros, Nikolaos, Schachner, Thomas, Sandner, Sigrid, Angleitner, Philipp, Bolotin, Gil, Jacobs, Stephan, Thielmann, Matthias, Wendt, Daniel, Choi, Yeong-Hoon, Liakopoulos, Oliver, Ohri, Sunil, Lipey, Alexander, Taggart, David P., Gavrilov, Yulia, Krasopoulos, George, Rajakaruna, Cha, Zacharias, Joseph, De Silva, Ravi, Channon, Keith M., Gehrig, Thomas, Donovan, Terrence John, and Friedrich, Ivar

Published
2022
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28. Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction (NIHR Health Informatics Collaborative: TROP-CABG study)

Author

Benedetto, Umberto, Sinha, Shubhra, Mulla, Abdulrahim, Glampson, Benjamin, Davies, Jim, Panoulas, Vasileios, Gautama, Sanjay, Papadimitriou, Dimitri, Woods, Kerrie, Elliott, Paul, Hemingway, Harry, Williams, Bryan, Asselbergs, Folkert W., Melikian, Narbeh, Krasopoulos, George, Sayeed, Rana, Wendler, Olaf, Baig, Kamran, Chukwuemeka, Andrew, Angelini, Gianni D., Sterne, Jonathan A.C., Johnson, Tom, Shah, Ajay M., Perera, Divaka, Patel, Riyaz S., Kharbanda, Rajesh, Channon, Keith M., Mayet, Jamil, and Kaura, Amit

Published
2022
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29. Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study

Author

Artico, Jessica, Shiwani, Hunain, Moon, James C., Gorecka, Miroslawa, McCann, Gerry P., Roditi, Giles, Morrow, Andrew, Mangion, Kenneth, Lukaschuk, Elena, Shanmuganathan, Mayooran, Miller, Christopher A., Chiribiri, Amedeo, Prasad, Sanjay K., Adam, Robert D., Singh, Trisha, Bucciarelli-Ducci, Chiara, Dawson, Dana, Knight, Daniel, Fontana, Marianna, Manisty, Charlotte, Treibel, Thomas A., Levelt, Eylem, Arnold, Ranjit, Macfarlane, Peter W., Young, Robin, McConnachie, Alex, Neubauer, Stefan, Piechnik, Stefan K., Davies, Rhodri H., Ferreira, Vanessa M., Dweck, Marc R., Berry, Colin, Greenwood, John P., Kelly, Bernard, Goreka, Miroslawa, Somers, Kathryn, Byrom-Goulthorp, Roo J., Anderson, Michelle, Britton, Laura, Richards, Fiona, Jones, Laura M., Moss, Alastair, Fisher, Jude, Wormleighton, Joanne, Parke, Kelly, Wright, Rachel, Yeo, Jian, Falconer, Judith, Harries, Valerie, Henderson, Paula, Newby, David, Popescu, Iulia, Zhang, Qiang, Raman, Betty, Channon, Keith, Krasopoulos, Catherine, Nunes, Claudia, Da Silva Rodrigues, Liliana, Nixon, Harriet, Panopoulou, Athanasia, Fletcher, Alison, Manley, Peter, Sykes, Robert, Fallon, Kirsty, Brown, Ammani, Kelly, Laura, McGinley, Christopher, Briscoe, Michael, Woodward, Rosemary, Hopkins, Tracey, McLennan, Evonne, Tynan, Nicola, Dymock, Laura, Swoboda, Peter, Wright, Judith, Exley, Donna, Steeds, Richard, Hutton, Kady, MacDonald, Sonia, Shetye, Abhishek, Orsborne, Christopher, Woodville-Jones, William, Ferguson, Susan, Bratis, Konstantinos, Fairbairn, Timothy, Sionas, Michail, Widdows, Peris, Gee Chew, Pei, Marsden, Christian, Collins, Tom, George, Linsha, Kearney, Lisa, Flett, Andrew, Smith, Simon, Zhenge, Alice, Harvey, Jake, Inacio, Liliana, Hanam-Penfold, Tomas, Gruner, Lucy, Razvi, Yousuf S.K., Crause, Jacolene, Davies, Nina M., Brown, James T., Chaco, Liza, Patel, Rishi, Kotecha, Tushar, Knight, Dan S., Green, Thomas, Ripley, David, Thompson, Maria, Cifra, Ugochi Akerele Elna, Alskaf, Ebraham, Crawley, Richard, Villa, Adriana, Nightingale, Angus K., Wright, Kim, Bonnick, Esther D., Hopkins, Emma, George, Jessy, Joseph, Linta, Cole, Graham, Vimalesvaran, Kavitha, Ali, Nadine, Carr, Caitlin R., Ross, Alexandra A.R., King, Clara, Farzad, Zohreh, Salmi, Sara A., Kirby, Kevin, McDiarmid, Adam, Stevenson, Hannah J., Matsvimbo, Pamela S., Joji, Lency, Fearby, Margaret, Brown, Benjamin, Bunce, Nicholas, Jennings, Robert, Sookhoo, Vennessa, Joshi, Shatabdi, Kanagala, Prathap, Fullalove, Sandra, Toohey, Catherine, Fenlon, Kate, Bellenger, Nicholas, He, Jingzhou, Statton, Sarah, Pamphilon, Nicola, Steele, Anna, Ball, Claire, McGahey, Ann, Balma, Silvia, Wilkes, Lynsey, Lewis, Katy, Walter, Michelle, Ionescu, Adrian, Ninan, Tishi, Richards, Suzanne, Williams, Marie, Alfakih, Khaled, Pilgrim, Samia, Joy, George, and Hussain, Ifza

Published
2023
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30. Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

Author

Dickinson, Yasmin, Boehni, Ruth, Obeid, Rima, Knapp, Jean-Pierre, Moser, Rudolf, Lewandowski, Adam J., Douglas, Gillian, Leeson, Paul, Channon, Keith M., and Chuaiphichai, Surawee

Abstract

BACKGROUND: Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. METHODS: We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. RESULTS: In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. CONCLUSIONS: Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Tetrahydrobiopterin and Nitric Oxide Synthase Recouplers

Author

Channon, Keith M., Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Rosenthal, Walter, Editorial Board Member, Wang, KeWei, Editorial Board Member, Schmidt, Harald H. H. W., editor, Ghezzi, Pietro, editor, and Cuadrado, Antonio, editor

Published
2021
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33. JCAD, a Gene at the 10p11 Coronary Artery Disease Locus, Regulates Hippo Signaling in Endothelial Cells.

Author

Jones, Peter, Kaiser, Michael, Ghaderi Najafabadi, Maryam, Koplev, Simon, Zhao, Yuqi, Douglas, Gillian, Kyriakou, Theodosios, Andrews, Sarah, Rajmohan, Rathinasabapathy, Watkins, Hugh, Channon, Keith, Ye, Shu, Yang, Xia, Björkegren, Johan, Samani, Nilesh, and Webb, Tom

Subjects
apoptosis, atherosclerosis, coronary artery disease, endothelium, phenotype, Adaptor Proteins, Signal Transducing, Apoptosis, Cell Adhesion, Cell Adhesion Molecules, Cell Movement, Cell Proliferation, Coculture Techniques, Coronary Artery Disease, HEK293 Cells, Hippo Signaling Pathway, Human Umbilical Vein Endothelial Cells, Humans, Monocytes, Neovascularization, Physiologic, Phenotype, Phosphoproteins, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases, Signal Transduction, THP-1 Cells, Transcription Factors, Tumor Suppressor Proteins, YAP-Signaling Proteins, rhoA GTP-Binding Protein
Abstract

Objective- A large number of genetic loci have been associated with risk of coronary artery disease (CAD) through genome-wide association studies, however, for most loci the underlying biological mechanism is unknown. Determining the molecular pathways and cellular processes affected by these loci will provide new insights into CAD pathophysiology and may lead to new therapies. The CAD-associated variants at 10p11.23 fall in JCAD, which encodes an endothelial junction protein, however, its molecular function in endothelial cells is not known. In this study, we characterize the molecular role of JCAD (junctional cadherin 5 associated) in endothelial cells. Approach and Results- We show that JCAD knockdown in endothelial cells affects key phenotypes related to atherosclerosis including proliferation, migration, apoptosis, tube formation, and monocyte binding. We demonstrate that JCAD interacts with LATS2 (large tumor suppressor kinase 2) and negatively regulates Hippo signaling leading to increased activity of YAP (yes-associated protein), the transcriptional effector of the pathway. We also show by double siRNA knockdown that the phenotypes caused by JCAD knockdown require LATS2 and that JCAD is involved in transmission of RhoA-mediated signals into the Hippo pathway. In human tissues, we find that the CAD-associated lead variant, rs2487928, is associated with expression of JCAD in arteries, including atherosclerotic arteries. Gene co-expression analyses across disease-relevant tissues corroborate our phenotypic findings and support the link between JCAD and Hippo signaling. Conclusions- Our results show that JCAD negatively regulates Hippo signaling in endothelial cells and we suggest that JCAD contributes to atherosclerosis by mediating YAP activity and contributing to endothelial dysfunction.

Published
2018

34. Hepatic miR-144 Drives Fumarase Activity Preventing NRF2 Activation During Obesity

Author

Azzimato, Valerio, Chen, Ping, Barreby, Emelie, Morgantini, Cecilia, Levi, Laura, Vankova, Ana, Jager, Jennifer, Sulen, André, Diotallevi, Marina, Shen, Joanne X., Miller, Anne, Ellis, Ewa, Rydén, Mikael, Näslund, Erik, Thorell, Anders, Lauschke, Volker M., Channon, Keith M., Crabtree, Mark J., Haschemi, Arvand, Craige, Siobhan M., Mori, Mattia, Spallotta, Francesco, and Aouadi, Myriam

Published
2021
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35. 51 Comparison of fully angiography derived versus hybrid of angiography and pressure wire derived assessment of coronary microvascular resistance: the OxAMI-hybrid study

Author

Chai, Jason, primary, Kotronias, Rafail, additional, Benenati, Stefano, additional, Chu, Miao, additional, Couch, Liam, additional, Marin, Federico, additional, Langrish, Jeremy, additional, Channon, Keith, additional, Banning, Adrian, additional, and De Maria, Giovanni, additional

Published
2024
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37. Changes in the investigation and management of suspected myocardial infarction and injury during COVID-19: a multi-centre study using routinely collected healthcare data

Author

Chammas, Lara, primary, Yuan, Kevin, additional, Little, Stephanie, additional, Roadknight, Gail, additional, Varnai, Kinga A., additional, Chang, Shing Chan, additional, Sze, Shirley, additional, Davies, Jim, additional, Tsui, Andrew, additional, Salih, Hizni, additional, Glampson, Ben, additional, Papadimitriou, Dimitri, additional, Mulla, Abdulrahim, additional, Woods, Kerrie, additional, O’Gallagher, Kevin, additional, Shah, Anoop D., additional, Williams, Bryan, additional, Asselbergs, Folkert W., additional, Mayer, Erik, additional, Lee, Richard, additional, Herbert, Christopher, additional, Johnson, Tom, additional, Grant, Stuart, additional, Curzen, Nick, additional, Shah, Ajay M., additional, Perera, Divaka, additional, Patel, Riyaz S., additional, Channon, Keith M., additional, Kaura, Amit, additional, Mayet, Jamil, additional, Eyre, David W., additional, Squire, Iain, additional, Kharbanda, Raj, additional, Lewis, Andrew, additional, and Wijesurendra, Rohan S., additional

Published
2024
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38. Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study

Author

Chan, Kenneth, primary, Wahome, Elizabeth, additional, Tsiachristas, Apostolos, additional, Antonopoulos, Alexios S, additional, Patel, Parijat, additional, Lyasheva, Maria, additional, Kingham, Lucy, additional, West, Henry, additional, Oikonomou, Evangelos K, additional, Volpe, Lucrezia, additional, Mavrogiannis, Michail C, additional, Nicol, Edward, additional, Mittal, Tarun K, additional, Halborg, Thomas, additional, Kotronias, Rafail A, additional, Adlam, David, additional, Modi, Bhavik, additional, Rodrigues, Jonathan, additional, Screaton, Nicholas, additional, Kardos, Attila, additional, Greenwood, John P, additional, Sabharwal, Nikant, additional, De Maria, Giovanni Luigi, additional, Munir, Shahzad, additional, McAlindon, Elisa, additional, Sohan, Yogesh, additional, Tomlins, Pete, additional, Siddique, Muhammad, additional, Kelion, Andrew, additional, Shirodaria, Cheerag, additional, Pugliese, Francesca, additional, Petersen, Steffen E, additional, Blankstein, Ron, additional, Desai, Milind, additional, Gersh, Bernard J, additional, Achenbach, Stephan, additional, Libby, Peter, additional, Neubauer, Stefan, additional, Channon, Keith M, additional, Deanfield, John, additional, Antoniades, Charalambos, additional, Thomas, Sheena, additional, Denton, Jon, additional, Farral, Robyn, additional, Taylor, Carolyn, additional, Qin, Wendy, additional, Kasongo, Mary, additional, Anthony, Susan, additional, Banning, Adrian, additional, Xie, Cheng, additional, Kharbanda, Rajesh K, additional, Pritchard, Amy, additional, Syed, Nigar, additional, Fry, Sam, additional, Mathers, Chris, additional, Rose, Anne, additional, Hudson, George, additional, Bajaj, Amrita, additional, Das, Intrajeet, additional, Deshpande, Aparna, additional, Rao, Praveen, additional, Lawday, Dan, additional, Mirsadraee, Saeed, additional, Hudson, Benjamin, additional, Berry, Colin, additional, Marwan, Mohamed, additional, Maurovich-Horvat, Pál, additional, He, Guo-Wei, additional, Lin, Wen-Hua, additional, Fan, Li-Juan, additional, Takahashi, Naohiko, additional, Kondo, Hidekazu, additional, Dai, Neng, additional, Ge, Junbo, additional, Koo, Bon-Kwon, additional, Guglielmo, Marco, additional, Pontone, Gianluca, additional, Huck, Daniel, additional, Benedek, Theodora, additional, Rajani, Ronak, additional, Vilic, Dijana, additional, Aljazzaf, Haleema, additional, Mun, Mak S, additional, Benedetti, Giulia, additional, Preston, Rebecca L, additional, Raisi-Estabragh, Zahra, additional, Connolly, Derek L, additional, Sharma, Vinoda, additional, Grenfell, Rebecca, additional, Bradlow, William, additional, Schmitt, Matthias, additional, Serfaty, Fabiano, additional, Gottlieb, Ilan, additional, Neves, Mario FT, additional, Newby, David E, additional, Dweck, Marc R, additional, Hatem, Stéphane, additional, Redheuil, Alban, additional, Benetos, Georgios, additional, Beer, Meinrad, additional, Granillo, Gastón AR, additional, Selvanayagam, Joseph, additional, Lopez-Jimenez, Francisco, additional, De Bosscher, Ruben, additional, Tavildari, Alain, additional, Figtree, Gemma, additional, Danad, Ibrahim, additional, Shantouf, Ronney, additional, Kietselaer, Bas, additional, Tousoulis, Dimitris, additional, Dangas, George, additional, Mehta, Nehal N, additional, Kontanidis, Christos, additional, Kunadian, Vijay, additional, and Fairbairn, Timothy A, additional

Published
2024
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39. The Role of Coronary Blood Flow and Myocardial Edema in the Pathophysiology of Takotsubo Syndrome

Author

Couch, Liam S., primary, Thomas, Katharine E., additional, Marin, Federico, additional, Terentes-Printzios, Dimitrios, additional, Kotronias, Rafail A., additional, Chai, Jason, additional, Lukaschuk, Elena, additional, Shanmuganathan, Mayooran, additional, Kellman, Peter, additional, Langrish, Jeremy P., additional, Channon, Keith M., additional, Neubauer, Stefan, additional, Piechnik, Stefan K., additional, Ferreira, Vanessa M., additional, de Maria, Giovanni Luigi, additional, and Banning, Adrian P., additional

Published
2024
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40. Comparison of troponin and natriuretic peptides in Takotsubo syndrome and acute coronary syndrome: a meta-analysis

Author

Couch, Liam Steven, primary, Garrard, James W, additional, Henry, John A, additional, Kotronias, Rafail A, additional, Alaour, Bashir, additional, De Maria, Giovanni Luigi, additional, Channon, Keith M, additional, Banning, Adrian P, additional, Lyon, Alexander Richard, additional, Marber, Michael, additional, and Kaier, Thomas Edward, additional

Published
2024
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41. Coronary Microvascular Dysfunction Assessed by Pressure Wire and CMR After STEMI Predicts Long-Term Outcomes

Author

Scarsini, Roberto, Shanmuganathan, Mayooran, De Maria, Giovanni Luigi, Borlotti, Alessandra, Kotronias, Rafail A., Burrage, Matthew K., Terentes-Printzios, Dimitrios, Langrish, Jeremy, Lucking, Andrew, Fahrni, Gregor, Cuculi, Florim, Ribichini, Flavio, Choudhury, Robin P., Kharbanda, Rajesh, Ferreira, Vanessa M., Channon, Keith M., and Banning, Adrian P.

Published
2021
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42. Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease

Author

Akawi, Nadia, Checa, Antonio, Antonopoulos, Alexios S., Akoumianakis, Ioannis, Daskalaki, Evangelia, Kotanidis, Christos P., Kondo, Hidekazu, Lee, Kirsten, Yesilyurt, Dilan, Badi, Ileana, Polkinghorne, Murray, Akbar, Naveed, Lundgren, Julie, Chuaiphichai, Surawee, Choudhury, Robin, Neubauer, Stefan, Channon, Keith M., Torekov, Signe S., Wheelock, Craig E., and Antoniades, Charalambos

Published
2021
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43. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

Author

Raman, Betty, Cassar, Mark Philip, Tunnicliffe, Elizabeth M., Filippini, Nicola, Griffanti, Ludovica, Alfaro-Almagro, Fidel, Okell, Thomas, Sheerin, Fintan, Xie, Cheng, Mahmod, Masliza, Mózes, Ferenc E., Lewandowski, Adam J., Ohuma, Eric O., Holdsworth, David, Lamlum, Hanan, Woodman, Myles J., Krasopoulos, Catherine, Mills, Rebecca, McConnell, Flora A. Kennedy, Wang, Chaoyue, Arthofer, Christoph, Lange, Frederik J., Andersson, Jesper, Jenkinson, Mark, Antoniades, Charalambos, Channon, Keith M., Shanmuganathan, Mayooran, Ferreira, Vanessa M., Piechnik, Stefan K., Klenerman, Paul, Brightling, Christopher, Talbot, Nick P., Petousi, Nayia, Rahman, Najib M., Ho, Ling-Pei, Saunders, Kate, Geddes, John R., Harrison, Paul J., Pattinson, Kyle, Rowland, Matthew J., Angus, Brian J., Gleeson, Fergus, Pavlides, Michael, Koychev, Ivan, Miller, Karla L., Mackay, Clare, Jezzard, Peter, Smith, Stephen M., and Neubauer, Stefan

Published
2021
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46. Mast cell–derived BH4 and serotonin are critical mediators of postoperative pain.

Author

Starkl, Philipp, Jonsson, Gustav, Artner, Tyler, Turnes, Bruna Lenfers, Gail, Laura-Marie, Oliveira, Tiago, Jain, Aakanksha, Serhan, Nadine, Stejskal, Karel, Lakovits, Karin, Hladik, Anastasiya, An, Meilin, Channon, Keith M., Kim, Hail, Köcher, Thomas, Weninger, Wolfgang, Stary, Georg, Knapp, Sylvia, Klang, Victoria, and Gaudenzio, Nicolas

Subjects
POSTOPERATIVE pain treatment, SUBSTANCE P receptors, MAST cells, TRYPTOPHAN hydroxylase, SUBSTANCE P
Abstract

Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of Gch1, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell–specific Gch1 or Tph1 showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P–driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment. Editor's summary: Inflammation caused by surgical tissue injury can evolve into chronic pain. Starkl et al. used a mouse model of surgical tissue injury to decipher a role for mast cell–derived metabolites in postoperative pain. Tetrahydrobiopterin (BH4) has been previously detected in injured nerves and correlates with pain intensity and is required for serotonin production by tryptophan hydroxylase (Tph1). Nerve-proximal mast cells were identified as a source of GTP cyclohydrolase 1 (Gch1), a rate-limiting enzyme for BH4 synthesis. Deletion of Gch1 or Tph1 from mast cells or mast cell depletion reduced tissue injury pain. The nociceptive neuropeptide substance P was detected at tissue injury sites and triggered BH4-dependent serotonin release from mast cells, thus defining how neuropeptides can act on mast cells and propagate pain responses. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Published
2024
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47. Emerging opportunities to target inflammation: myocardial infarction and type 2 diabetes.

Author

Kufazvinei, Tafadzwa T J, Chai, Jason, Boden, Katherine A, Channon, Keith M, and Choudhury, Robin P

Subjects
TYPE 2 diabetes, MYOCARDIAL infarction, CORONARY artery disease, OVERALL survival, HEALING
Abstract

After myocardial infarction (MI), patients with type 2 diabetes have an increased rate of adverse outcomes, compared to patients without. Diabetes confers a 1.5–2-fold increase in early mortality and, importantly, this discrepancy has been consistent over recent decades, despite advances in treatment and overall survival. Certain assumptions have emerged to explain this increased risk, such as differences in infarct size or coronary artery disease severity. Here, we re-evaluate that evidence and show how contemporary analyses using state-of-the-art characterization tools suggest that the received wisdom tells an incomplete story. Simultaneously, epidemiological and mechanistic biological data suggest additional factors relating to processes of diabetes-related inflammation might play a prominent role. Inflammatory processes after MI mediate injury and repair and are thus a potential therapeutic target. Recent studies have shown how diabetes affects immune cell numbers and drives changes in the bone marrow, leading to pro-inflammatory gene expression and functional suppression of healing and repair. Here, we review and re-evaluate the evidence around adverse prognosis in patients with diabetes after MI, with emphasis on how targeting processes of inflammation presents unexplored, yet valuable opportunities to improve cardiovascular outcomes in this vulnerable patient group. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Ly6C hi Monocytes Are Metabolically Reprogrammed in the Blood during Inflammatory Stimulation and Require Intact OxPhos for Chemotaxis and Monocyte to Macrophage Differentiation.

Author

Purvis, Gareth S. D., McNeill, Eileen, Wright, Benjamin, Channon, Keith M., and Greaves, David R.

Subjects
MONOCYTES, MACROPHAGES, CHEMOTAXIS, ELECTRON transport, PHENOTYPIC plasticity, TRANSCRIPTOMES
Abstract

Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a coordinated and precise manner. Here, we investigate the origin and transcriptional reprogramming of monocytes using a model of acute inflammation, zymosan-induced peritonitis. Monocyte trafficking and adoptive transfer experiments confirmed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single-cell transcriptomics revealed significant heterogeneity within the surface marker-defined CD11b+Ly6G−Ly6Chi monocyte populations within the blood and at the site of inflammation. We show that two major transcriptional reprogramming events occur during the initial six hours of Ly6Chi monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events. Experimentally, we demonstrate that OxPhos via the intact mitochondrial electron transport chain is essential for murine and human monocyte chemotaxis. Moreover, OxPhos is needed for monocyte-to-macrophage differentiation and macrophage M(IL-4) polarisation. These new findings from transcriptional profiling open up the possibility that shifting monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Automated CMR Index of Left Ventricular Diastolic Function Post-acute Myocardial Infarction Provides Independent and Incremental Prediction of Long-term Prognosis When Added to Conventional Indices

Author

Shanmuganathan, Mayooran, primary, Gonzales, Ricardo, additional, Burrage, Matthew, additional, Arvidsson, Per, additional, Banerjee, Abhirup, additional, Cakir, Irem, additional, Seemann, Felicia, additional, Heiberg, Einar, additional, Peters, Dana, additional, Zhang, Qiang, additional, Channon, Keith, additional, Piechnik, Stefan, additional, and Ferreira, Vanessa, additional

Published
2024
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