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190 results on '"Shirodaria, Cheerag"'

1. 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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2. 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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3. 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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4. 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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6. Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: a pilot randomized, double-blind placebo-controlled trial.

Author

Farina, Christopher J, Davidson, Michael H, Shah, Prediman K, Stark, Charles, Lu, Wenqi, Shirodaria, Cheerag, Wright, Timothy, Antoniades, Charalambos A, Nilsson, Jan, and Mehta, Nehal N

Subjects
ATHEROSCLEROTIC plaque, ATP-binding cassette transporters, LIPOPROTEIN A, INFLAMMATION, DISEASE risk factors
Abstract

A pilot randomized, double-blind placebo-controlled trial was conducted to assess the effects of orticumab, a monoclonal antibody that targets oxidized low-density lipoprotein (oxLDL), on coronary inflammation in patients with psoriasis. The study found that treatment with orticumab reduced the Fat Attenuation Index (FAI) score, a measure of coronary inflammation, in patients with high levels of inflammation but had no effect in those with low levels of inflammation. The study suggests that targeting oxLDL with orticumab may reduce coronary inflammation and potentially lower the risk of fatal cardiac events in patients with elevated inflammation. However, further research is needed to fully understand the mechanisms and clinical implications of this treatment. [Extracted from the article]

Published
2024
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11. 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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12. Abstract 21015: Coronary Inflammation in Humans Drives Spatial Changes of Perivascular Adipose Tissue Composition Detectable by a Novel Computed Tomography-Based Technology

Author

Antonopoulos, Alexios S, Oikonomou, Evangelos K, Sanna, Fabio, Sabharwal, Nikant, Thomas, Sheena, Herdman, Laura, Margaritis, Marios, Shirodaria, Cheerag, Kampoli, Anna-Maria, Akoumianakis, Ioannis, Petrou, Mario, Sayeed, Rana, Krasopoulos, George, Psarros, Constantinos, Ciccone, Patricia, Brophy, Carl M, Digby, Janet, Kelion, Andrew, Uberoi, Raman, Anthony, Suzan, Alexopoulos, Nikolaos, Tousoulis, Dimitris, Achenbach, Stephan, Neubauer, Stefan, Channon, Keith M, and Antoniades, Charalambos

Published
2017

13. Abstract 11962: Applying a Deep-Learning Approach for Automated Quantification of Epicardial Adipose Tissue on Coronary Computed Tomography Angiography in Challenging Clinical Populations

Author

West, Henry W, primary, Siddique, Muhammad, additional, Volpe, Lucrezia, additional, Desai, Ria, additional, Lyasheva, Maria, additional, Dangas, Katerina, additional, Shirodaria, Cheerag, additional, Neubauer, Stefan, additional, Channon, Keith M, additional, Desai, Milind Y, additional, Williams, Michelle C, additional, Rodrigues, Jonathan C, additional, Adlam, David, additional, Ed, Nicol D, additional, and Antoniades, Charalambos, additional

Published
2021
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14. Abstract 13475: Epicardial Adiposity Measured by a Deep Learning Network, Predicts Mortality and Cardiovascular Events in Patients Undergoing Cardiac CT

Author

West, Henry W, primary, Williams, Michelle C, additional, Siddique, Muhammad, additional, Volpe, Lucrezia, additional, Desai, Ria, additional, Lyasheva, Maria, additional, Dangas, Katerina, additional, Tomlins, Pete, additional, Oikonomou, Evangelos K, additional, Shirodaria, Cheerag, additional, Neubauer, Stefan, additional, Channon, Keith M, additional, Rodrigues, Jonathan, additional, Nicol, Ed, additional, Newby, David E, additional, and Antoniades, Charalambos, additional

Published
2021
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15. A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute stemi patients undergoing primary PCI

Author

Dhil, David Adlam, primary, Zarebinski, Maciej, additional, Uren, Neal G., additional, Ptaszynski, Pawel, additional, Oldroyd, Keith G., additional, Munir, Shahzad, additional, Zaman, Azfar, additional, Contractor, Hussain, additional, Kiss, Róbert Gábor, additional, Édes, István, additional, Szachniewicz, Joanna, additional, Nagy, Gergely Gyorgy, additional, Garcia, Mario J., additional, Tomcsanyi, János, additional, Irving, John, additional, Sharp, Andrew S.P., additional, Musialek, Piotr, additional, Lupkovics, Géza, additional, Shirodaria, Cheerag, additional, Selvanayagam, Joseph B., additional, Quinn, Pauline, additional, Ng, Leong, additional, Roth, Mark, additional, Insko, Michael A., additional, Haber, Ben, additional, Hill, Stephen, additional, Siegel, Lori, additional, Tulloch, Simon, additional, and Channon, Keith M., additional

Published
2021
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16. Standardized measurement of coronary inflammation using cardiovascular computed tomography: integration in clinical care as a prognostic medical device

Author

Oikonomou, Evangelos K, primary, Antonopoulos, Alexios S, additional, Schottlander, David, additional, Marwan, Mohammad, additional, Mathers, Chris, additional, Tomlins, Pete, additional, Siddique, Muhammad, additional, Klüner, Laura V, additional, Shirodaria, Cheerag, additional, Mavrogiannis, Michail C, additional, Thomas, Sheena, additional, Fava, Agostina, additional, Deanfield, John, additional, Channon, Keith M, additional, Neubauer, Stefan, additional, Desai, Milind Y, additional, Achenbach, Stephan, additional, and Antoniades, Charalambos, additional

Published
2021
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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. Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

Author

Antonopoulos, Alexios S., Margaritis, Marios, Coutinho, Patricia, Shirodaria, Cheerag, Psarros, Costas, Herdman, Laura, Sanna, Fabio, De Silva, Ravi, Petrou, Mario, Sayeed, Rana, Krasopoulos, George, Lee, Regent, Digby, Janet, Reilly, Svetlana, Bakogiannis, Constantinos, Tousoulis, Dimitris, Kessler, Benedikt, Casadei, Barbara, Channon, Keith M., and Antoniades, Charalambos

Published
2015
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20. GCH1 Haplotype Determines Vascular and Plasma Biopterin Availability in Coronary Artery Disease: Effects on Vascular Superoxide Production and Endothelial Function

Author

Antoniades, Charalambos, Shirodaria, Cheerag, Van Assche, Tim, Cunnington, Colin, Tegeder, Irmgard, Lötsch, Jörn, Guzik, Tomasz J., Leeson, Paul, Diesch, Jonathan, Tousoulis, Dimitris, Stefanadis, Christodoulos, Woolf, Clifford J., Alp, Nicholas J., Channon, Keith M., and Costigan, Michael

Published
2008
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25. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: Rationale and design of the ODYSSEY Outcomes trial

Author

Schwartz, Gregory G., Bessac, Laurence, Berdan, Lisa G., Bhatt, Deepak L., Bittner, Vera, Diaz, Rafael, Goodman, Shaun G., Hanotin, Corinne, Harrington, Robert A., Jukema, Wouter J., Mahaffey, Kenneth W., Moryusef, Angèle, Pordy, Robert, Roe, Matthew T., Rorick, Tyrus, Sasiela, William J., Shirodaria, Cheerag, Szarek, Michael, Tamby, Jean-François, Tricoci, Pierluigi, White, Harvey, Zeiher, Andreas, and Steg, Philippe Gabriel

Published
2014
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31. 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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32. Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index

Author

Elnabawi, Youssef A., primary, Oikonomou, Evangelos K., additional, Dey, Amit K., additional, Mancio, Jennifer, additional, Rodante, Justin A., additional, Aksentijevich, Milena, additional, Choi, Harry, additional, Keel, Andrew, additional, Erb-Alvarez, Julie, additional, Teague, Heather L., additional, Joshi, Aditya A., additional, Playford, Martin P., additional, Lockshin, Benjamin, additional, Choi, Andrew D., additional, Gelfand, Joel M., additional, Chen, Marcus Y., additional, Bluemke, David A., additional, Shirodaria, Cheerag, additional, Antoniades, Charalambos, additional, and Mehta, Nehal N., additional

Published
2019
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33. TREATMENT WITH BIOLOGIC THERAPY IN PSORIASIS IS ASSOCIATED WITH A REDUCTION IN CORONARY ARTERY INFLAMMATION, ASSESSED BY PERIVASCULAR FAT ATTENUATION INDEX

Author

Elnabawi, Youssef, primary, Oikonomou, Evangelos, additional, Dey, Amit, additional, Mancio, Jennifer, additional, Rodante, Justin, additional, Gelfand, Joel, additional, Chen, Marcus, additional, Bluemke, David, additional, Shirodaria, Cheerag, additional, Antoniades, Charalambos, additional, and Mehta, Nehal, additional

Published
2019
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34. Multimodal cardiovascular magnetic resonance quantifies regional variation in vascular structure and function in patients with coronary artery disease: Relationships with coronary disease severity

Author

Kylintireas Ilias, Shirodaria Cheerag, Lee Justin MS, Cunningon Colin, Lindsay Alistair, Francis Jane, Robson Matthew D, Neubauer Stefan, Channon Keith M, and Choudhury Robin P

Subjects
Atherosclerosis, magnetic resonance imaging, coronary artery disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Cardiovascular magnetic resonance (CMR) of the vessel wall is highly reproducible and can evaluate both changes in plaque burden and composition. It can also measure aortic compliance and endothelial function in a single integrated examination. Previous studies have focused on patients with pre-identified carotid atheroma. We define these vascular parameters in patients presenting with coronary artery disease and test their relations to its extent and severity. Methods and Results 100 patients with CAD [single-vessel (16%); two-vessel (39%); and three-vessel (42%) non-obstructed coronary arteries (3%)] were studied. CAD severity and extent was expressed as modified Gensini score (mean modified score 12.38 ± 5.3). A majority of carotid plaque was located in the carotid bulb (CB). Atherosclerosis in this most diseased segment correlated modestly with the severity and extent of CAD, as expressed by the modified Gensini score (R = 0.251, P < 0.05). Using the AHA plaque classification, atheroma class also associated with CAD severity (rho = 0.26, P < 0.05). The distal descending aorta contained the greatest plaque, which correlated with the degree of CAD (R = 0.222; P < 0.05), but with no correlation with the proximal descending aorta, which was relatively spared (R = 0.106; P = n. s.). Aortic distensibility varied along its length with the ascending aorta the least distensible segment. Brachial artery FMD was inversely correlated with modified Gensini score (R = -0.278; P < 0.05). In multivariate analysis, distal descending aorta atheroma burden, distensibility of the ascending aorta, carotid atheroma class and FMD were independent predictors of modified Gensini score. Conclusions Multimodal vascular CMR shows regional abnormalities of vascular structure and function that correlate modestly with the degree and extent of CAD.

Published
2011
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36. A Bleeding Kiss: intramural haematoma secondary to balloon angioplasty

Author

Van Gaal William J, Shirodaria Cheerag, and Banning Adrian P

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Intramural coronary haematoma following percutaneous coronary intervention in the absence of coronary dissection is a rare phenomenon. Case presentation A 69 year old lady with previous prosthetic aortic valve replacement underwent percutaneous coronary intervention (PCI) from the left mainstem to the left anterior descending artery (LAD) and kissing balloon inflations to the LAD and circumflex (Cx) arteries. Although intravascular ultrasound examination (IVUS) of both the LAD and Cx showed both vessels to be widely patent at the end of the procedure, she developed ischaemic chest pain six hours later. Repeat coronary angiography revealed a significant stenosis in the proximal Cx vessel, which was confirmed on IVUS to be intramural haematoma. Conclusion In patients taking warfarin in addition to standard antiplatelet therapy, kissing balloon inflations should be carried out with caution.

Published
2007
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37. Detecting human coronary inflammation by imaging perivascular fat

Author

Antonopoulos, Alexios S. Sanna, Fabio Sabharwal, Nikant and Thomas, Sheena Oikonomou, Evangelos K. Herdman, Laura and Margaritis, Marios Shirodaria, Cheerag Kampoli, Anna-Maria and Akoumianakis, Ioannis Petrou, Mario Sayeed, Rana and Krasopoulos, George Psarros, Constantinos Ciccone, Patricia and Brophy, Carl M. Digby, Janet Kelion, Andrew Uberoi, Raman and Anthony, Suzan Alexopoulos, Nikolaos Tousoulis, Dimitris and Achenbach, Stephan Neubauer, Stefan Channon, Keith M. and Antoniades, Charalambos

Abstract

Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis method and studied CT images of human adipose tissue explants from 453 patients undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan information on the biology of the explants. We developed an imaging metric, the CT fat attenuation index (FAI), that describes adipocyte lipid content and size. The FAI has excellent sensitivity and specificity for detecting tissue inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a validation cohort of 273 subjects, the FAI gradient around human coronary arteries identified early subclinical coronary artery disease in vivo, as well as detected dynamic changes of PVAT in response to variations of vascular inflammation, and inflamed, vulnerable atherosclerotic plaques during acute coronary syndromes. Our study revealed that human vessels exert paracrine effects on the surrounding PVAT, affecting local intracellular lipid accumulation in preadipocytes, which can be monitored using a CT imaging approach. This methodology can be implemented in clinical practice to noninvasively detect plaque instability in the human coronary vasculature.

Published
2017

38. 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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40. Detecting human coronary inflammation by imaging perivascular fat

Author

Antonopoulos, Alexios S., primary, Sanna, Fabio, additional, Sabharwal, Nikant, additional, Thomas, Sheena, additional, Oikonomou, Evangelos K., additional, Herdman, Laura, additional, Margaritis, Marios, additional, Shirodaria, Cheerag, additional, Kampoli, Anna-Maria, additional, Akoumianakis, Ioannis, additional, Petrou, Mario, additional, Sayeed, Rana, additional, Krasopoulos, George, additional, Psarros, Constantinos, additional, Ciccone, Patricia, additional, Brophy, Carl M., additional, Digby, Janet, additional, Kelion, Andrew, additional, Uberoi, Raman, additional, Anthony, Suzan, additional, Alexopoulos, Nikolaos, additional, Tousoulis, Dimitris, additional, Achenbach, Stephan, additional, Neubauer, Stefan, additional, Channon, Keith M., additional, and Antoniades, Charalambos, additional

Published
2017
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41. Predictive value of telomere length on outcome following acute myocardial infarction: evidence for contrasting effects of vascular vs. blood oxidative stress

Author

Margaritis, Marios, primary, Sanna, Fabio, additional, Lazaros, George, additional, Akoumianakis, Ioannis, additional, Patel, Sheena, additional, Antonopoulos, Alexios S., additional, Duke, Chloe, additional, Herdman, Laura, additional, Psarros, Costas, additional, Oikonomou, Evangelos K., additional, Shirodaria, Cheerag, additional, Petrou, Mario, additional, Sayeed, Rana, additional, Krasopoulos, George, additional, Lee, Regent, additional, Tousoulis, Dimitris, additional, Channon, Keith M., additional, and Antoniades, Charalambos, additional

Published
2017
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42. Turnaround at UCLH: A hospital in intensive care case (D)

Author

Jacobides, Michael, Devlin, Anita, Shirodaria, Cheerag, and Verheul, Renate

Subjects
FOS: Economics and business
Abstract

University College London Hospital NHS Foundation Trust (UCLH) is a major London teaching hospital. It encountered serious financial problems as a result of the consolidation of two separate hospitals into one new hospital building, coupled with a change in the remuneration system for NHS hospitals. The turnaround took place between April 2005 and May 2007. Pelham Allen was appointed Turnaround Director by the NHS regulator to implement a recovery plan that stabilized the situation and laid the foundations for long-term operational and financial success. This case gives the reader a close-up view of one of the largest, most sensitive and most successful UK public sector turnarounds in recent years, and highlights the similarities with, and differences from, private sector turnarounds. The case also examines the different approaches that turnaround managers can take to embed change when in a position of influence., LBS Case Code: CS-10-023

Published
2010
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43. Turnaround at UCLH: A hospital in intensive care case (A) and (B)

Author

Jacobides, Michael, Devlin, Anita, Shirodaria, Cheerag, and Verheul, Renate

Subjects
FOS: Economics and business
Abstract

University College London Hospital NHS Foundation Trust (UCLH) is a major London teaching hospital. It encountered serious financial problems as a result of the consolidation of two separate hospitals into one new hospital building, coupled with a change in the remuneration system for NHS hospitals. The turnaround took place between April 2005 and May 2007. Pelham Allen was appointed Turnaround Director by the NHS regulator to implement a recovery plan that stabilized the situation and laid the foundations for long-term operational and financial success. This case gives the reader a close-up view of one of the largest, most sensitive and most successful UK public sector turnarounds in recent years, and highlights the similarities with, and differences from, private sector turnarounds. The case also examines the different approaches that turnaround managers can take to embed change when in a position of influence., LBS Case Code: CS-10-016

Published
2010
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44. Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

Author

Antonopoulos, Alexios S., primary, Margaritis, Marios, additional, Coutinho, Patricia, additional, Shirodaria, Cheerag, additional, Psarros, Costas, additional, Herdman, Laura, additional, Sanna, Fabio, additional, De Silva, Ravi, additional, Petrou, Mario, additional, Sayeed, Rana, additional, Krasopoulos, George, additional, Lee, Regent, additional, Digby, Janet, additional, Reilly, Svetlana, additional, Bakogiannis, Constantinos, additional, Tousoulis, Dimitris, additional, Kessler, Benedikt, additional, Casadei, Barbara, additional, Channon, Keith M., additional, and Antoniades, Charalambos, additional

Published
2014
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47. MTHFR 677 C > T Polymorphism Reveals Functional Importance for 5-Methyltetrahydrofolate, Not Homocysteine, in Regulation of Vascular Redox State and Endothelial Function in Human Atherosclerosis

Author

Antoniades, Charalambos Shirodaria, Cheerag Leeson, Paul and Baarholm, Otto A. Van-Assche, Tim Cunnington, Colin Pillai, Ravi Ratnatunga, Chandi Tousoulis, Dimitris Stefanadis, Christodoulos Refsum, Helga Channon, Keith M.

Abstract

Background-The role of circulating homocysteine as an atherosclerosis risk factor has recently been questioned. However, 5-methyl-tetrahydrofolate (5-MTHF), the circulating metabolite of folic acid participating in homocysteine metabolism, has direct effects on vascular function. We sought to distinguish the effects of plasma versus vascular tissue 5-MTHF and homocysteine on vascular redox and endothelial nitric oxide bioavailability in human vessels. Methods and Results-We used the methyl tetrahydrofolate reductase (MTHFR) gene polymorphism 677C>T as a model of chronic exposure of the vascular wall to varying 5-MTHF levels in 218 patients undergoing coronary artery bypass graft surgery. Vascular superoxide, vascular 5-MTHF, and total homocysteine were determined in saphenous veins and internal mammary arteries obtained during surgery. Nitric oxide bioavailability was evaluated by organ bath studies on saphenous vein rings. MTHFR genotype was a determinant of vascular 5-MTHF (not vascular homocysteine). Both MTHFR genotype and vascular 5-MTHF were associated with vascular nitric oxide bioavailability and superoxide generated by uncoupled endothelial nitric oxide synthase. In contrast, vascular homocysteine was associated only with NADPH-stimulated superoxide. Conclusions-Genetic polymorphism 677 C>T on MTHFR affects vascular 5-MTHF (but not homocysteine) and can be used as a model to distinguish the chronic effects of vascular 5-MTHF from homocysteine on vascular wall. Vascular 5-MTHF, rather than plasma or vascular homocysteine, is a key regulator of endothelial nitric oxide synthase coupling and nitric oxide bioavailability in human vessels, suggesting that plasma homocysteine is an indirect marker of 5-MTHF rather than a primary regulator of endothelial function. (Circulation. 2009; 119: 2507-2515.)

Published
2009

48. Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis

Author

Antoniades, Charalambos Shirodaria, Cheerag Leeson, Paul and Antonopoulos, Alexios Warrick, Nicholas Van-Assche, Tim and Cunnington, Colin Tousoulis, Dimitris Pillai, Ravi and Ratnatunga, Chandi Stefanadis, Christodoulos Channon, Keith M.

Abstract

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), is considered to be a risk factor for atherosclerosis. However, the mechanisms relating ADMA with vascular function have been evaluated in vitro and in animal models, but its effect in human vasculature is unclear. We examined the impact of serum ADMA on endothelial nitric oxide (NO) bioavailability and vascular superoxide radical (O2-) production in patients with advanced atherosclerosis. Paired samples of saphenous veins (SVs) and internal mammary arteries (IMAs) were collected from 201 patients undergoing coronary bypass surgery, and serum ADMA was measured pre-operatively. The vasomotor responses of SV segments to acetylcholine (ACh) and bradykinin (Bk) were evaluated ex vivo. Vascular O2- was measured in paired SV and IMA by lucigenin-enhanced chemiluminescence. The l-NAME-inhibitable as well as the NADPH-stimulated vascular O2- generation was also determined by chemiluminescence. High serum ADMA levels were associated with decreased vasorelaxation of SV to ACh (P < 0.05) and Bk (P < 0.05). Similarly, high serum ADMA was associated with higher total O2- production in both SVs and IMAs (P < 0.05) and greater l-NAME-inhibitable vascular O2- (P < 0.05). However, serum ADMA was not associated with NADPH-stimulated vascular O2-. In multivariable linear regression, serum ADMA was independently associated with vascular O2- in both SVs [beta (SE): 0.987 (0.412), P = 0.019] and IMAs [beta (SE): 1.905 (0.541), P = 0.001]. Asymmetrical dimethylarginine was also independently associated with maximum vasorelaxation in response to both ACh [beta (SE): 14.252 (3.976), P = 0.001] and Bk [beta (SE): 9.564 (3.762), P = 0.013]. This is the first study that demonstrates an association between ADMA and important measures of vascular function, such as vascular O2- production and NO bioavailability directly in human vessels. Although serum ADMA has no effect on NADPH-stimulated superoxide in intact vessels, it is associated with greater eNOS uncoupling in the human vascular endothelium of patients with coronary artery disease.

Published
2009

49. GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease - Effects on vascular superoxide production and endothelial function

Author

Antoniades, Charalambos Shirodaria, Cheerag Van Assche, Tim and Cunnington, Colin Tegeder, Irmgard Loetsch, Joern Guzik, Tomasz J. Leeson, Paul Diesch, Jonathan Tousoulis, Dimitris and Stefanadis, Christodoulos Costigan, Michael Woolf, Clifford J. Alp, Nicholas J. Channon, Keith M.

Abstract

Objectives This study sought to determine the effects of endogenous tetrahydrobiopterin (BH4) bioavailability on endothelial nitric oxide synthase (eNOS) coupling, nitric oxide (NO) bioavailability, and vascular superoxide production in patients with coronary artery disease (CAD). Background GTP-cyclohydrolase I, encoded by the GCH1 gene, is the rate-limiting enzyme in the biosynthesis of BH4, an eNOS cofactor important for maintaining enzymatic coupling. We examined the associations between haplotypes of the GCH1 gene, GCH1 expression and biopterin levels, and the effects on endothelial function and vascular superoxide production. Methods Blood samples and segments of internal mammary arteries and saphenous veins were obtained from patients with CAD undergoing coronary artery bypass grafting (n = 347). The GCH1 haplotypes were defined by 3 polymorphisms: rs8007267G < A, rs3783641A < T, and rs10483639C < G (X haplotype: A, T, G; O haplotype: any other combination). Vascular superoxide (+/- the eNOS inhibitor NG-nitro-L-arginine methyl ester [L-NAME]) was measured by lucigenin-enhanced chemiluminescence, whereas the vasorelaxations of saphenous veins to acetylcholine were evaluated ex vivo. Results Haplotype frequencies were OO 70.6%, XO 27.4%, and XX 2.0%. The X haplotype was associated with significantly lower vascular GCH1 messenger ribonucleic acid expression and substantial reductions in both plasma and vascular BH4 levels. In X haplotype carriers both vascular superoxide and L-NAME-inhibitable superoxide were significantly increased, and were associated with reduced vasorelaxations to acetylcholine. Conclusions GCH1 gene expression, modulated by a particular GCH1 haplotype, is a major determinant of BH4 bioavailability both in plasma and in the vascular wall in patients with CAD. Genetic variation in GCH1 underlies important differences in endogenous BH4 availability and is a determinant of eNOS coupling, vascular redox state, and endothelial function in human vascular disease.

Published
2008

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