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36 results on '"Kotanidis, Christos P."'

1. 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

3. 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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4. 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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6. 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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7. Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome: individual patient data meta-analysis

Author

Kotanidis, Christos P, primary, Mills, Gregory B, additional, Bendz, Bjørn, additional, Berg, Erlend S, additional, Hildick-Smith, David, additional, Hirlekar, Geir, additional, Milasinovic, Dejan, additional, Morici, Nuccia, additional, Myat, Aung, additional, Tegn, Nicolai, additional, Sanchis, Juan, additional, Savonitto, Stefano, additional, De Servi, Stefano, additional, Fox, Keith A A, additional, Pocock, Stuart, additional, and Kunadian, Vijay, additional

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

Author

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

Published
2022
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17. Effects of canagliflozin on human myocardial redox signalling: clinical implications

Author

Kondo, Hidekazu, primary, Akoumianakis, Ioannis, additional, Badi, Ileana, additional, Akawi, Nadia, additional, Kotanidis, Christos P, additional, Polkinghorne, Murray, additional, Stadiotti, Ilaria, additional, Sommariva, Elena, additional, Antonopoulos, Alexios S, additional, Carena, Maria C, additional, Oikonomou, Evangelos K, additional, Reus, Elsa Mauricio, additional, Sayeed, Rana, additional, Krasopoulos, George, additional, Srivastava, Vivek, additional, Farid, Shakil, additional, Chuaiphichai, Surawee, additional, Shirodaria, Cheerag, additional, Channon, Keith M, additional, Casadei, Barbara, additional, and Antoniades, Charalambos, additional

Published
2021
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18. Cardiac Magnetic Resonance to Detect the Underlying Substrate in Patients with Frequent Idiopathic Ventricular Arrhythmias

Author

Nikolaidou, Chrysovalantou, primary, Kotanidis, Christos P., additional, Wijesurendra, Rohan, additional, Leal-Pelado, Joana, additional, Kouskouras, Konstantinos, additional, Vassilikos, Vassilios P., additional, Karvounis, Haralambos, additional, Ntusi, Ntobeko, additional, Antoniades, Charalambos, additional, Neubauer, Stefan, additional, and Karamitsos, Theodoros D., additional

Published
2021
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19. D Radiotranscriptomic analysis of perivascular adipose tissue quantifies vascular inflammation in covid-19 from routine CT angiograms: Stratification of “new UK variant” Infection and prediction of in-hospital outcomes

Author

Kotanidis, Christos P, primary, Xie, Cheng, additional, Adlam, David, additional, Rodrigues, Jonathan CL, additional, Siddique, Muhammad, additional, Lockstone, Helen, additional, Thomas, Sheena, additional, Kotronias, Rafail, additional, Oikonomou, Evangelos K, additional, Lumley, Sheila F, additional, Neubauer, Stefan, additional, Newby, David E, additional, Channon, Keith M, additional, Deanfield, John, additional, and Antoniades, Charalambos, additional

Published
2021
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21. Perivascular Fat Attenuation Index Stratifies Cardiac Risk Associated With High-Risk Plaques in the CRISP-CT Study

Author

Oikonomou, Evangelos K., primary, Desai, Milind Y., additional, Marwan, Mohamed, additional, Kotanidis, Christos P., additional, Antonopoulos, Alexios S., additional, Schottlander, David, additional, Channon, Keith M., additional, Neubauer, Stefan, additional, Achenbach, Stephan, additional, and Antoniades, Charalambos, additional

Published
2020
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22. Adipose tissue-derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

Author

Akoumianakis, Ioannis Sanna, Fabio Margaritis, Marios Badi, Ileana Akawi, Nadia Herdman, Laura Coutinho, Patricia and Fagan, Harry Antonopoulos, Alexios S. Oikonomou, Evangelos K. and Thomas, Sheena Chiu, Amy P. Chuaiphichai, Surawee and Kotanidis, Christos P. Christodoulides, Constantinos Petrou, Mario Krasopoulos, George Sayeed, Rana Lv, Lei Hale, Ashley Kararoudi, Meisam Naeimi McNeill, Eileen Douglas, Gillian George, Sarah Tousoulis, Dimitris Channon, Keith M. and Antoniades, Charalambos

Subjects
embryonic structures, sense organs
Abstract

Obesity is associated with changes in the secretome of adipose tissue (AT), which affects the vasculature through endocrine and paracrine mechanisms. Wingless-related integration site 5A (WNT5A) and secreted frizzled-related protein 5 (SFRP5), adipokines that regulate noncanonical Wnt signaling, are dysregulated in obesity. We hypothesized that WNT5A released from AT exerts endocrine and paracrine effects on the arterial wall through noncanonical RAC1-mediated Wnt signaling. In a cohort of 1004 humans with atherosclerosis, obesity was associated with increased WNT5A bioavailability in the circulation and the AT, higher expression of WNT5A receptors Frizzled 2 and Frizzled 5 in the human arterial wall, and increased vascular oxidative stress due to activation of NADPH oxidases. Plasma concentration of WNT5A was elevated in patients with coronary artery disease compared to matched controls and was independently associated with calcified coronary plaque progression. We further demonstrated that WNT5A induces arterial oxidative stress and redox-sensitive migration of vascular smooth muscle cells via Frizzled 2-mediated activation of a previously uncharacterized pathway involving the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) and the GTPase RAC1. Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans.

Published
2019

23. Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

Author

Akoumianakis, Ioannis, primary, Sanna, Fabio, additional, Margaritis, Marios, additional, Badi, Ileana, additional, Akawi, Nadia, additional, Herdman, Laura, additional, Coutinho, Patricia, additional, Fagan, Harry, additional, Antonopoulos, Alexios S., additional, Oikonomou, Evangelos K., additional, Thomas, Sheena, additional, Chiu, Amy P., additional, Chuaiphichai, Surawee, additional, Kotanidis, Christos P., additional, Christodoulides, Constantinos, additional, Petrou, Mario, additional, Krasopoulos, George, additional, Sayeed, Rana, additional, Lv, Lei, additional, Hale, Ashley, additional, Naeimi Kararoudi, Meisam, additional, McNeill, Eileen, additional, Douglas, Gillian, additional, George, Sarah, additional, Tousoulis, Dimitris, additional, Channon, Keith M., additional, and Antoniades, Charalambos, additional

Published
2019
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24. A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography

Author

Oikonomou, Evangelos K, primary, Williams, Michelle C, additional, Kotanidis, Christos P, additional, Desai, Milind Y, additional, Marwan, Mohamed, additional, Antonopoulos, Alexios S, additional, Thomas, Katharine E, additional, Thomas, Sheena, additional, Akoumianakis, Ioannis, additional, Fan, Lampson M, additional, Kesavan, Sujatha, additional, Herdman, Laura, additional, Alashi, Alaa, additional, Centeno, Erika Hutt, additional, Lyasheva, Maria, additional, Griffin, Brian P, additional, Flamm, Scott D, additional, Shirodaria, Cheerag, additional, Sabharwal, Nikant, additional, Kelion, Andrew, additional, Dweck, Marc R, additional, Van Beek, Edwin J R, additional, Deanfield, John, additional, Hopewell, Jemma C, additional, Neubauer, Stefan, additional, Channon, Keith M, additional, Achenbach, Stephan, additional, Newby, David E, additional, and Antoniades, Charalambos, additional

Published
2019
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27. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data

Author

Oikonomou, Evangelos K, primary, Marwan, Mohamed, additional, Desai, Milind Y, additional, Mancio, Jennifer, additional, Alashi, Alaa, additional, Hutt Centeno, Erika, additional, Thomas, Sheena, additional, Herdman, Laura, additional, Kotanidis, Christos P, additional, Thomas, Katharine E, additional, Griffin, Brian P, additional, Flamm, Scott D, additional, Antonopoulos, Alexios S, additional, Shirodaria, Cheerag, additional, Sabharwal, Nikant, additional, Deanfield, John, additional, Neubauer, Stefan, additional, Hopewell, Jemma C, additional, Channon, Keith M, additional, Achenbach, Stephan, additional, and Antoniades, Charalambos, additional

Published
2018
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30. Osteoprotegerin increases parallel to insulin resistance in obese adolescents.

Author

Kotanidou, Eleni P., Kotanidis, Christos P., Giza, Styliani, Serbis, Anastasios, Tsinopoulou, Vasiliki-Regina, Karalazou, Paraskevi, Tzimagiorgis, Georgios, and Galli-Tsinopoulou, Assimina

Subjects
*INSULIN resistance, *NF-kappa B, *TUMOR necrosis factor receptors, *OSTEOPROTEGERIN, *ADOLESCENT obesity
Abstract

Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). Material and Methods: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. Results: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents' subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. Conclusions: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation. [ABSTRACT FROM AUTHOR]

Published
2019
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32. Abstract 12842: Adipose Tissue Derived Ceramides Regulate the Myocardial Redox State and Predict Cardiovascular Outcomes

Author

Polkinghorne, Murray D, Akawi, Nadia, Badi, Ileana, Checa, Antonio, Kotanidis, Christos, Akoumianakis, Ioannis, Antonopoulos, Alexios S, Krasopoulos, George, Sayeed, Rana, Walcot, Nicholas, Channon, Keith M, Wheelock, Craig, and Antoniades, Charalambos

Abstract

Introduction:Ceramides biosynthesis is dysregulated in obesity, yet their role as mediators of obesity-induced myocardial dysfunction is unclear.Objective:We investigate the causal role of AT-derived ceramides in regulating the myocardial redox state and explore their prognostic value in patients with CVD.Methods:In 880 cardiac surgery patients, 20 sphingolipids were measured in plasma, subcutaneous-, thoracic- and epicardial-AT biopsies and their secretomes. Myocardial redox state was measured and the contribution of NOXs, uncoupled eNOS and mitochondrial oxidases to O2.-production quantified. Median follow-up was 8.3 years. Genetic variants were identified to predict CVD outcomes using cis-Mendelian Randomisation. The underlying mechanisms were explored using differentiated H9c2 cardiomyocytes in vitroand human myocardial tissue ex vivo.Results:C16:0-ceramide (CerC16) was the most abundant ceramide secreted from AT (p<0.0001). Patients with high plasma CerC16 and C16:0-glucosylceramide (GlcC16) had significantly increased myocardial O2.-production (vs low/int.) (A). Patients with rs112572487(B), an intronic SNP in UGCG, had significantly increased plasma GlcC16 (C)and myocardial NOX-derived O2.-(D)vs those without. Exogenous CerC16 (20nM) induced O2.-production in H9c2 cardiomyocytes and human myocardial tissue (E), an effect prevented by the UGCGinhibitor D-PDMP. Importantly, high plasma GlcC16 led to a higher risk of cardiac death and/or heart failure (HR=2.128 [1.101, 4.115], p=0.025) vs low/int. levels, a relationship also seen with rs112572487 (F). rs112572487 also led to an increased risk of new, post-operative atrial fibrillation in hospital (HR=1.805 [1.188, 2.742], p=0.006).Conclusions:We demonstrate for the first time, that AT-derived ceramides are causally related with dysregulated myocardial redox signalling and adverse cardiovascular disease outcomes in patients with advanced atherosclerosis.

Published
2022
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33. Abstract 12000: A Novel Human Arterial Transcriptomic Signature Associated With Major Adverse Cardiovascular Events and Oxidative Stress

Author

Kotanidis, Christos, Lockstone, Helen, Wright, Benjamin, Akawi, Nadia, Akoumianakis, Ioannis, Badi, Ileana, Polkinghorne, Murray, Farid, Shakil, Srivastava, Vivek, Krasopoulos, George, Channon, Keith M, and Antoniades, Charalambos

Abstract

Introduction:The biology of human vascular wall is implicated in cardiovascular pathology. We applied discovery transcriptomics to internal mammary arteries (IMAs) obtained from cardiac surgery patients, to identify pathways that can be treated therapeutically.Methods:Weighted correlation network analysis was conducted in sequencing data from IMAs RNA in 205 patients (Arm 1). Association with future incidence of major adverse cardiovascular events [MACE: cardiovascular death (CVD), non-fatal myocardial infarction or stroke, or new-onset heart failure] was assessed with Cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, and plasma TNFa). Arm 2 included 497 patients in whom segments of IMA were used for ex-vivo quantification of NADPH-stimulated superoxide by lucigenin chemiluminescence.Results:We identified 10 coexpressed gene ‘modules’ in the human arterial wall, through unsupervised transcriptomic analysis. The “red” module was found to cluster with arterial NADPH oxidase activity, while its eigengene values had the most significant correlation (a). Patients with high eigengene values for the “red” module showed a 3-fold higher risk of MACE (b), and enrichment analysis revealed top pathways (c). The Study Arm 2 population was followed up for a median of 6.35 years [IQR: 3.97-8.38], with 50 CVD and 101 MACE. High NADPH oxidases activity was independently predictive of cardiovascular mortality (d) and MACE (adj. hazard ratio 1.58 [1.07-2.36], p=0.02).Conclusion:We demonstrate that arterial oxidative stress leads to high risk of MACE in patients with atherosclerosis. We also identify a novel, redox-related arterial transcriptomic signature that predicts long-term cardiovascular risk. Pathways related with oxidative stress, or glucose metabolism or Hypoxia-Inducible Factor-1 in the human arterial wall, may be rational therapeutic targets to reduce cardiovascular risk in secondary prevention.

Published
2021
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35. Abstract 12286: Adipose Tissue Ceramides Reduces Endothelium-Dependent Vasorelaxation, Amplifies Vascular Oxidative Stress & Induces Systemic Inflammation Ultimately Leading To Death In Coronary Artery Disease

Author

Akawi, Nadia, Checa, Antonio, Akoumianakis, Ioannis, Margaritis, Marios, Kotanidis, Christos P, Daskalakis, Evangelia, Kondo, Hidekazu, Channon, Keith M, Wheelock, Craig, and Antoniades, Charalambos

Abstract

Introduction:Adipose tissue (AT) is a metabolically active organ secreting a wide spectrum of bioactive compounds affecting the cardiovascular system.Hypothesis:We hypothesize that AT dysregulated secretions in coronary artery disease (CAD) impose a direct detrimental effect on vascular health contributing to disease pathogenesis and progression.Methods:Untargeted metabolomics of the secretomes of paired thoracic and subcutaneous AT samples from 48 patients undergoing cardiac surgery selected retrospectively from the OxHVF study was performed using LC/MS. Sphingolipids were quantified in 96 AT and 633 plasma samples of the OxHVF participants using targeted LC/MS. Superoxide (O2.-) was measured in patients? vessels and in human aortic endothelial cells (HAEC) using lucigenin-enhanced chemiluminescence. Vasorelaxations of vessels? rings in response to acetylcholine were evaluated in an ex-vivo organ-bath setting.Results:Metabolomics differential and enrichment analyses highlighted the significant differences in sphingolipids secretion levels between the two fat depots. C16-ceramide evidently the most abundant differentially secreted ceramide from the thoracic depot (A). Higher levels of thoracic AT ceramides were significantly associated with enhanced vascular O2.-production (B)and reduced endothelium-dependent vascular relaxation (C). Circulating C16-ceramide positively correlated with thoracic AT ceramides synthesis (D),vascular oxidative stress (E), inflammation and death [adjusted hazard ratio = 3.17 with 95% Cl 1.1-9.2] strikingly when presented as a ratio against C24-ceramide (F). In HAEC, exogenous ceramide treatment increased intracellular O2.-via endothelial nitric oxide synthase.Conclusions:In this study, we demonstrate for the first time that higher AT ceramides synthesis is associated with pathological vascular redox states and an elevation in circulating C16-ceramide in patients with CAD.

Published
2019
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36. Abstract 14695: Oxidative Stress in the Myocardium as a Novel Predictor of Long-Term Outcomes in Patients Undergoing Cardiac Surgery

Author

Kotanidis, Christos P, Antonopoulos, Alexios S, Oikonomou, Evangelos K, Akoumianakis, Ioannis, Badi, Ileana, Krasopoulos, George, Sayeed, Rana, Petrou, Mario, Srivastava, Vivek, Farid, Shakil, Galiatsatos, Nikolaos, Channon, Keith M, and Antoniades, Charalambos

Abstract

Introduction:Oxidative stress in the myocardium has been linked with adverse short-term clinical outcomes after cardiac surgery, but its prognostic value for long-term results is unknown.Hypothesis:Myocardial NADPH oxidase activity is a predictor of long-term outcomes in cardiac surgical patients.Methods:In total, 216 patients from the Oxford Heart Vessels and Fat (Ox-HVF) cohort were enrolled. Myocardial superoxide (O2.) quantification was performed using lucigenin-enhanced chemiluminescence and specific contribution of NADPH oxidase was quantified as the Vas287021-inhibitable signal following NADPH stimulation (Vas2870 is a pan-NADPH oxidase inhibitor). Malonyldialdehyde (MDA), hsCRP and BNP were measured in plasma collected pre-operatively. Patients were followed-up for a mean of 2.9?1.4 years for the primary combined endpoint of cardiovascular mortality or new onset heart failure.Results:Myocardial oxidative stress was not correlated with baseline systemic oxidative stress (MDA, A), systemic inflammation (hsCRP, B) or BNP levels (C). In univariate analyses, MDA, hsCRP and BNP were not associated with cardiovascular mortality or new onset heart failure (D). NADPH oxidase activity, however, was predictive of the combined endpoint, and cardiovascular mortality alone (HR[95%CI]: 1.53[1.10-2.13], p=0.01) but not all-cause mortality (HR[95%CI]: 1.32[0.96-1.80], p=0.08). These associations remained significant after adjustment for EuroSCORE II and BNP (HR[95%CI]: 1.80[1.20-2.70], p=0.004). Patient survival was significantly lower in the high vs. low NADPH oxidase activity subgroup (E). Adding NADPH oxidase activity to a baseline clinical model improved model?s performance (p=0.01).Conclusion:Increased myocardial NADPH oxidase activity independently predicts long-term outcomes, suggesting that myocardial protection against oxidative stress may constitute a rational therapeutic target in cardiac surgical patients.

Published
2019
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