| Title: |
Basic science * 232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function |
| Authors: |
Heathfield, Sarah; Parker, Ben; Zeef, Leo; Bruce, Ian; Alexander, Yvonne; Collins, Fraser; Stone, Michael; Wang, Edward; Williams, Anwen S.; Wright, Helen L.; Thomas, Huw B.; Moots, Robert J.; Edwards, Steven W.; Bullock, Craig; Chapman, Victoria; Walsh, David A.; Mobasheri, Ali; Kendall, David; Kelly, Sara; Bayley, Rachel; Buckley, Chris D.; Young, Stephen P.; Rump-Goodrich, Lisa; Middleton, Jim; Chen, Liye; Fisher, Roman; Kollnberger, Simon; Shastri, Nilabh; Kessler, Benedikt M.; Bowness, Paul; Nazeer Moideen, Abdul; Evans, Laura; Osgood, Louise; Jones, Simon A.; Nowell, Mari A.; Mahadik, Younis; Young, Stephen; Morgan, Matthew; Gordon, Caroline; Harper, Lorraine; Giles, Joanna L.; Paul Morgan, B.; Harris, Claire L.; Rysnik, Oliwia J.; McHugh, Kirsty; Payeli, Sravan; Marroquin, Osiris; Shaw, Jacqueline; Renner, Christoph; Nayar, Saba; Cloake, Tom; Bombardieri, Michele; Pitzalis, Costantino; Buckley, Chris; Barone, Francesca; Lane, Peter; Coles, Mark; Williams, Emma L.; Edwards, Christopher J.; Cooper, Cyrus; Oreffo, Richard O.; Dunn, Sara; Crawford, Aileen; Wilkinson, Mark; Le Maitre, Christine; Bunning, Rowena; Daniels, Jodie; Phillips, Kate L. E.; Chiverton, Neil; Le Maitre, Christine L.; Shaw, Jackie; Ridley, Anna; Wong-Baeza, Isabel; Keidel, Sarah; Chan, Antoni; Gullick, Nicola J.; Abozaid, Hanan S.; Jayaraj, David M.; Evans, Hayley G.; Scott, David L.; Choy, Ernest H.; Taams, Leonie S.; Hickling, M.; Golor, G.; Jullion, A.; Shaw, S.; Kretsos, K.; Bari, Syed F.; Rhys-Dillon, Brian; Amos, Nicholson; Siebert, Stefan; Bunning, Rowena D.; Haddock, Gail; Cross, Alison K.; Kate, I; Phillips, E.; Cross, Alison; Bunning, Rowena A. D.; Ceeraz, Sabrina; Spencer, Jo; Choy, Ernest; Corrigall, Valerie; Crilly, Anne; Palmer, Helen; Lockhart, John; Plevin, Robin; Ferrell, William R.; McInnes, Iain; Hutchinson, David; Perry, Liz; DiCicco, Maria; Humby, Frances; Kelly, Stephen; Hands, Rebecca; McInnes, Ian; Taylor, Peter; Mehta, Puja; Mitchell, Adam; Tysoe, Carolyn; Caswell, Richard; Owens, Martina; Vincent, Tonia; Hashmi, Tahir M.; Price-Forbes, Alec; Sharp, Charlotte A.; Murphy, Helen; Wood, Elizabeth F.; Doherty, Teresa; Sheldon, Jo; Sofat, Nidhi; Goff, Iain; Platt, Philip N.; Abdulkader, Rita; Clunie, Gavin; Ismajli, Mediola; Nikiphorou, Elena; Young, Adam; Tugnet, Nicola; Dixey, Josh; Banik, Snehashish; Alcorn, Desmond; Hunter, John; Win Maw, Win; Patil, Pravin; Hayes, Fiona; Main Wong, Way; Borg, Frances A.; Dasgupta, Bhaskar; Malaviya, Anshuman P.; Ostor, Andrew J.; Chana, Jasroop K.; Ahmed, Azeem A.; Edmonds, Sally; Coward, Lucy; Borg, Frances; Heaney, Jonathan; Amft, Nicole; Simpson, John; Dhillon, Veena; Ayalew, Yezenash; Khattak, Fazlihakim; Gayed, Mary; Amarasena, Roshan I.; McKenna, Frank; Mc Laughlin, Maeve; Baburaj, Krishnan; Fattah, Zozik; Ng, Nora; Wilson, Jo; Colaco, Bernard; Williams, Mark R.; Adizie, Tochukwu; Casey, Matthew; Lip, Stefanie; Tan, Shaun; Anderson, David; Robertson, Calum; Devanny, Ian; Field, Max; Walker, David; Robinson, Sandra; Ryan, Sarah; Hassell, Andrew; Bateman, James; Allen, Maggie; Davies, David; Crouch, Carina; Walker-Bone, Karen; Gainsborough, Nicola; Lutalo, Pamela M.; Davies, Ursula M.; Mckew, Jennifer R.; Millar, Auleen M.; Wright, Stephen A.; Bell, Aubrey L.; Thapper, Muryum; Roussou, Thalia; Cumming, Jo; Hull, Richard G.; McKeogh, John; O'Connor, Mortimer B.; Hassan, Ahmed I.; Bond, Ursula; Swan, Joan; Phelan, Mark J.; Coady, David; Kumar, Namita; Farrow, Luke; Bukhari, Marwan; Oldroyd, Alexander G.; Greenbank, Cathi; McBeth, John; Duncan, Rosie; Brown, Deborah; Horan, Michael; Pendleton, Neil; Littlewood, Alison; Cordingley, Lis; Mulvey, Matthew; Curtis, Elizabeth M.; Cole, Zoe A.; Crozier, Sarah R.; Georgia, Ntani; Robinson, Siân M.; Godfrey, Keith M.; Sayer, Avan A.; Inskip, Hazel M.; Harvey, Nicholas C.; Davies, Rebecca; Mercer, Louise; Galloway, James; Low, Audrey; Watson, Kath; Lunt, Mark; BSRBR Control Centre Consortium; Symmons, Deborah; Hyrich, Kimme; On Behalf of the BSRBR; Chitale, Sarang; Estrach, Cristina; Goodson, Nicola J.; Rankin, Elizabeth; Jiang, C. Q.; Cheng, K. K.; Lam, T. H.; Adab, Peymané; Ling, Stephanie; Humphreys, Jennifer; Ellis, Corrinne; Bunn, Diane; Verstappen, Suzanne M.; Fluess, Elisa; Macfarlane, Gary J.; Bond, Christine; Jones, Gareth T.; Scott, Ian C.; Steer, Sophia; Lewis, Cathryn M.; Cope, Andrew; Mulvey, Matthew R.; Lovell, Karina; Keeley, Philip; Woby, Steve; Beasley, Marcus; Viatte, Sebastien; Plant, Darren; Fu, Bo; Solymossy, Csilla; Worthington, Jane; Barton, Anne; Williams, Frances M.; Osei-Bordom, Daniel-Clement; Popham, Maria; MacGregor, Alex; Spector, Tim; Little, Jayne; Herrick, Ariane; Pushpakom, S.; Ennis, H.; McBurney, H.; Worthington, J.; Newman, W.; Ibrahim, Ibrahim; Morgan, Anne; Wilson, Anthony; Isaacs, John; Sanderson, Tessa; Hewlett, Sarah; Calnan, Michael; Morris, Marianne; Raza, Karim; Kumar, Kanta; Cardy, Caroline M.; Pauling, John D.; Jenkins, Jessica; Brown, Sue J.; McHugh, Neil; Mugford, Miranda; Davies, Charlotte; Cooper, Nicola; Brooksby, Alan; Dures, Emma; Ambler, Nick; Fletcher, Debbie; Pope, Denise; Robinson, Frances; Rooke, Royston; Gorman, Claire L.; Reynolds, Piero; Hakim, Alan J.; Bosworth, Ailsa; Weaver, Dan; Kiely, Patrick D.; Skeoch, Sarah; Jani, Meghna; Amarasena, Roshan; Rao, Chandini; Macphie, Elizabeth; McLoughlin, Yokemei; Shah, Preeti; Else, Sara; Semenova, Olga; Thompson, Helen; Ogunbambi, Olabambo; Kallankara, Sathish; Patel, Yusuf; Baguley, Elaine; Halsey, John; Severn, Andrew; Selvan, Shilpa; Price, Elizabeth; Husain, Muhammad J.; Brophy, Sinead; Phillips, Ceri J.; Cooksey, Roxanne; Irvine, Elizabeth; Lendrem, Dennis; Mitchell, Sheryl; Bowman, Simon; Pease, Colin T.; Emery, Paul; Andrews, Jacqueline; Sutcliffe, Nurhan; Lanyon, Peter; Gupta, Monica; McLaren, John; Regan, Marian; Cooper, Annie; Giles, Ian; Isenberg, David; Griffiths, Bridget; Foggo, Heather; Edgar, Suzanne; Vadivelu, Saravanan; Ng, Wan-Fai; Iqbal, Itrat; Heron, Louise; Pilling, Claire; Marks, Jonathan; Hull, Richard; Ledingham, Jo; Han, Chenglong; Gathany, Tim; Tandon, Neeta; Hsia, Elizabeth; Taylor, P.; Strand, V.; Sensky, T.; Harta, N.; Fleming, S.; Kay, Lesley; Rutherford, Michelle; Nicholl, Karl; Eyre, Tracey; Wilson, Gillian; Johnson, Phil; Russell, M.; Timoshanko, J.; Duncan, G.; Spandley, A.; Roskell, S.; West, Louise; Adshead, Rebecca; Donnelly, Simon P.; Ashton, Simon; Tahir, Hasan; Patel, Dipti; Darroch, James; Boulton, John; Ellis, Benjamin; Finlay, Ron; Murray-Brown, William; Priori, R.; Tappuni, T.; Vartoukian, S.; Seoudi, N.; Picarelli, G.; Fortune, F.; Valesini, G.; Pitzalis, C.; Bombardieri, M.; Ball, Elisabeth; Rooney, Madeleine; Bell, Aubrey; Mérida, Angeles Acosta; Tarelli, Edward; Axford, John; Pericleous, Charis; Pierangeli, Silvia S.; Ioannou, John; Rahman, Anisur; Alavi, Azita; Hughes, Michael; Evans, Bronwen; Zaki, Awal; Hui, Michelle; Garner, Rozeena; Rees, Frances; Bavakunji, Riaz; Daniel, Priya; Varughese, Sneha; Srikanth, Asha; Andres, Mariano; Pearce, Fiona; Leung, Jansen; Lim, Ken; Oomatia, Amin; Petri, Michelle; Fang, Hong; Birnbaum, Julius; Amissah-Arthur, Maame; Stewart, Kirsty; Jennens, Hannah; Braude, Simon; Sutton, Emily J.; Watson, Kath D.; Yee, Chee-Seng; Jayne, David; Akil, Mohammed; Ahmad, Yasmeen; D'Cruz, David; Khamashta, Munther; Teh, Lee-Suan; Zoma, Asad; Dey, Ida D.; Kenu, Ernest; Garza-Garcia, Acely; Murfitt, Lucy; Driscoll, Paul C.; Pierangeli, Silvia; Ioannou, Yiannis; Reynolds, John A.; Ray, David W.; O'Neill, Terence; Segeda, Iuliia; Shevchuk, Sergii; Kuvikova, Inna; Brown, Nina; Venning, Michael; Dhanjal, Mandish; Mason, Justin; Nelson-Piercy, Catherine; Basu, Neil; Paudyal, Priya; Stockton, Marie; Lawton, Sally; Dent, Caroline; Kindness, Kathy; Meldrum, Gillian; John, Elizabeth; Arthur, Catherine; West, Lucy; Macfarlane, Matthew V.; Reid, David M.; Yates, Max; Loke, Yoon; Watts, Richard; Christidis, Dimitrios; Williams, Mark; Sivakumar, Rajappa; Misra, Ramnath; Danda, Debashish; Mahendranath, K. M.; Bacon, Paul A.; Mackie, Sarah L. |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2012 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
POSTER VIEWING III (THURSDAY 3 MAY) |
| Description: |
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q < 0.00005). This was supported by qPCR analysis at 6 hrs (E-selectin and VCAM-1; 208.5 fold and 40.5, respectively above control) and also at 1, 3 and 24 hrs (E-selectin; 25.6, 93.5, 12.7 fold, respectively) (VCAM-1; 4.7, 47.2, 17.6 fold) (n = 3; p < 0.05). In contrast, HAoECs treated with TNF in combination with CZP exhibited control levels of E-selectin and VCAM-1 transcript (p > 0.2 compared to control; p > 0.05 compared to TNF ... |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://rheumatology.oxfordjournals.org/cgi/content/short/51/suppl_3/iii140; http://dx.doi.org/10.1093/rheumatology/kes108 |
| DOI: |
10.1093/rheumatology/kes108 |
| Availability: |
http://rheumatology.oxfordjournals.org/cgi/content/short/51/suppl_3/iii140; https://doi.org/10.1093/rheumatology/kes108 |
| Rights: |
Copyright (C) 2012, British Society for Rheumatology |
| Accession Number: |
edsbas.3E7A20B1 |
| Database: |
BASE |