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3. Optimization of pharmacotherapies for ambulatory patients with heart failure and reduced ejection fraction is associated with improved outcomes

Author

Jarjour, Marilyne, Leclerc, Jacinthe, Bouabdallaoui, Nadia, Ahnadi, Charaf, Brouillette, Denis, de Denus, Simon, Fortier, Annik, Garceau, Patrick, Giraldeau, Geneviève, Lepage, Serge, Liszkowski, Mark, O'Meara, Eileen, Parent, Marie-Claude, Racine, Normand, Tremblay-Gravel, Maxime, White, Michel, Rouleau, Jean-Lucien, and Ducharme, Anique

Published
2023
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5. Time in Therapeutic Range With Vitamin K Antagonists in Congenital Heart Disease: A Multicentre Study

Author

Basmaji, Samir, Samuel, Michelle, Shohoudi, Azadeh, Hamilton, Robert M., Aboulhosn, Jamil, Broberg, Craig S., Chaix, Marie-A, Cohen, Scott, Cook, Stephen, Dore, Annie, Fernandes, Susan M., Fortier, Annik, Fournier, Anne, Guertin, Marie-Claude, Kay, Joseph, Mondésert, Blandine, Mongeon, François-Pierre, Opotowsky, Alexander R., Proietti, Anna, Ting, Jennifer, Zaidi, Ali, and Khairy, Paul

Published
2022
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9. “Impact of Nociception Level (NOL) index intraoperative guidance of fentanyl administration on opioid consumption, postoperative pain scores and recovery in patients undergoing gynecological laparoscopic surgery. A randomized controlled trial”

Author

Espitalier, Fabien, Idrissi, Moulay, Fortier, Annik, Bélanger, Marie-Ève, Carrara, Lucie, Dakhlallah, Sarah, Rivard, Chantal, Brulotte, Véronique, Zaphiratos, Valérie, Loubert, Christian, Godin, Nadia, Fortier, Louis-Philippe, Verdonck, Olivier, and Richebé, Philippe

Published
2021
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12. A randomized controlled trial comparing nociception level (NOL) index, blood pressure, and heart rate responses to direct laryngoscopy versus videolaryngoscopy for intubation: the NOLint project

Author

Sbeghen, Virginie, Verdonck, Olivier, McDevitt, Jason, Zaphiratos, Valérie, Brulotte, Véronique, Loubert, Christian, Tanoubi, Issam, Drolet, Pierre, Belanger, Marie-Eve, Fortier, Louis-Philippe, Godin, Nadia, Guertin, Marie-Claude, Fortier, Annik, and Richebé, Philippe

Published
2021
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21. Erector spinae plane block did not improve postoperative pain-related outcomes and recovery after video-assisted thoracoscopic surgery : a randomised controlled double-blinded multi-center trial

Author

Clairoux, Ariane, primary, Moore, Alex, additional, Caron-Goudreau, Maxime, additional, Soucy-Proulx, Maxim, additional, Thibault, Maxime, additional, Brulotte, Véronique, additional, Bélanger, Marie-Ève, additional, Raft, Julien, additional, Godin, Nadia, additional, Idrissi, Moulay, additional, Desroches, Julie, additional, Ruel, Monique, additional, Fortier, Annik, additional, and Richebé, Philippe, additional

Published
2023
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29. PO-02-106 GENERAL ANESTHESIA VERSUS CONSCIOUS SEDATION WITH LOCOREGIONAL ANESTHESIA IN S-ICD IMPLANTATION: A MONOCENTRIC RETROSPECTIVE ANALYSIS

Author

De Marco, Corrado, primary, Lebon, Jean-Sébastien, additional, Rousseau-Saine, Nicolas, additional, Dubuc, Marc, additional, Thibault, Bernard, additional, CADRIN-TOURIGNY, JULIA, additional, Raymond-Paquin, Alexandre, additional, Chabot-Blanchet, Malorie, additional, Fortier, Annik, additional, and Mondesert, Blandine A., additional

Published
2023
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41. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Author

Cadrin-Tourigny, Julia, Bosman, Laurens P., Nozza, Anna, Wang, Weijia, Tadros, Rafik, Bhonsale, Aditya, Bourfiss, Mimount, Fortier, Annik, Lie, Oyvind H., Saguner, Ardan M., Svensson, Anneli, Andorin, Antoine, Tichnell, Crystal, Murray, Brittney, Zeppenfeld, Katja, van den Berg, Maarten P., Asselbergs, Folkert W., Wilde, Arthur A. M., Krahn, Andrew D., Talajic, Mario, Rivard, Lena, Chelko, Stephen, Zimmerman, Stefan L., Kamel, Ihab R., Crosson, Jane E., Judge, Daniel P., Yap, Sing-Chien, van der Heijden, Jeroen F., Tandri, Harikrishna, Jongbloed, Jan D. H., Guertin, Marie-Claude, van Tintelen, J. Peter, Platonov, Pyotr G., Duru, Firat, Haugaa, Kristina H., Khairy, Paul, Hauer, Richard N. W., Calkins, Hugh, te Riele, Anneline S. J. M., James, Cynthia A., Cadrin-Tourigny, Julia, Bosman, Laurens P., Nozza, Anna, Wang, Weijia, Tadros, Rafik, Bhonsale, Aditya, Bourfiss, Mimount, Fortier, Annik, Lie, Oyvind H., Saguner, Ardan M., Svensson, Anneli, Andorin, Antoine, Tichnell, Crystal, Murray, Brittney, Zeppenfeld, Katja, van den Berg, Maarten P., Asselbergs, Folkert W., Wilde, Arthur A. M., Krahn, Andrew D., Talajic, Mario, Rivard, Lena, Chelko, Stephen, Zimmerman, Stefan L., Kamel, Ihab R., Crosson, Jane E., Judge, Daniel P., Yap, Sing-Chien, van der Heijden, Jeroen F., Tandri, Harikrishna, Jongbloed, Jan D. H., Guertin, Marie-Claude, van Tintelen, J. Peter, Platonov, Pyotr G., Duru, Firat, Haugaa, Kristina H., Khairy, Paul, Hauer, Richard N. W., Calkins, Hugh, te Riele, Anneline S. J. M., and James, Cynthia A.

Abstract

Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 +/- 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion Using the Largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com)., Funding Agencies|Canadian Heart Rhythm Society George Mines Traveling Fellowship; Montreal Heart Institute Foundation; Fondation LeducqLeducq Foundation [16 CVD 02]; Dutch Heart FoundationNetherlands Heart Foundation [2015T058, CVON2015-12 eDETECT, 2012-10 PREDICT]; Netherlands Organisation for Scientific ResearchNetherlands Organization for Scientific Research (NWO) [040.11.586]; Netherlands Heart Institute [06901]; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [320030_160327]; UMC Utrecht 2017 Alexandre Suerman Stipend; UMC Utrecht Fellowship Clinical Research Talent; European Unions Horizon 2020 research and innovation program under the ERA-NET Co-fund action [680969]; Dr Francis P. Chiaramonte Private Foundation; Leyla Erkan Family Fund for ARVD Research; Dr Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins; Bogle Foundation; Healing Hearts Foundation; Campanella family; Patrick J. Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments; Georg und Bertha Schwyzer-Winiker Foundation; Baugarten Foundation; Swiss Heart Foundation; Leonie-Wild Foundation; Marvin and Philippa Carsley Chair of Medicine; UCL Hospitals NIHR Biomedical Research Centre

Published
2022
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42. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Author

Arts Assistenten Cardiologie, Cardiologie zorg, Team Medisch, Circulatory Health, Genetica Groep Van Tintelen, Cancer, Child Health, Genetica, Onderzoek Precision medicine, Cadrin-Tourigny, Julia, Bosman, Laurens P., Nozza, Anna, Wang, Weijia, Tadros, Rafik, Bhonsale, Aditya, Bourfiss, Mimount, Fortier, Annik, Lie, Øyvind H., Saguner, Ardan M., Svensson, Anneli, Andorin, Antoine, Tichnell, Crystal, Murray, Brittney, Zeppenfeld, Katja, Van Den Berg, Maarten P., Asselbergs, Folkert W., Wilde, Arthur A.M., Krahn, Andrew D., Talajic, Mario, Rivard, Lena, Chelko, Stephen, Zimmerman, Stefan L., Kamel, Ihab R., Crosson, Jane E., Judge, Daniel P., Yap, Sing Chien, Van Der Heijden, Jeroen F., Tandri, Harikrishna, Jongbloed, Jan D.H., Guertin, Marie Claude, Van Tintelen, J. Peter, Platonov, Pyotr G., Duru, Firat, Haugaa, Kristina H., Khairy, Paul, Hauer, Richard N.W., Calkins, Hugh, Te Riele, Anneline S.J.M., James, Cynthia A., Arts Assistenten Cardiologie, Cardiologie zorg, Team Medisch, Circulatory Health, Genetica Groep Van Tintelen, Cancer, Child Health, Genetica, Onderzoek Precision medicine, Cadrin-Tourigny, Julia, Bosman, Laurens P., Nozza, Anna, Wang, Weijia, Tadros, Rafik, Bhonsale, Aditya, Bourfiss, Mimount, Fortier, Annik, Lie, Øyvind H., Saguner, Ardan M., Svensson, Anneli, Andorin, Antoine, Tichnell, Crystal, Murray, Brittney, Zeppenfeld, Katja, Van Den Berg, Maarten P., Asselbergs, Folkert W., Wilde, Arthur A.M., Krahn, Andrew D., Talajic, Mario, Rivard, Lena, Chelko, Stephen, Zimmerman, Stefan L., Kamel, Ihab R., Crosson, Jane E., Judge, Daniel P., Yap, Sing Chien, Van Der Heijden, Jeroen F., Tandri, Harikrishna, Jongbloed, Jan D.H., Guertin, Marie Claude, Van Tintelen, J. Peter, Platonov, Pyotr G., Duru, Firat, Haugaa, Kristina H., Khairy, Paul, Hauer, Richard N.W., Calkins, Hugh, Te Riele, Anneline S.J.M., and James, Cynthia A.

Published
2022

44. Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in atheroprotection

Author

Rautureau, Yohann, primary, Berlatie, Marianne, additional, Rivas, Daniel, additional, Uy, Kurunradeth, additional, Blanchette, Alexandre, additional, Miquel, Géraldine, additional, Higgins, Marie-Ève, additional, Mecteau, Mélanie, additional, Nault, Audrey, additional, Villeneuve, Louis, additional, Lavoie, Véronique, additional, Théberge-Julien, Gabriel, additional, Brand, Geneviève, additional, Lapointe, Line, additional, Denis, Maxime, additional, Rosa, Camille, additional, Fortier, Annik, additional, Blondeau, Lucie, additional, Guertin, Marie-Claude, additional, Dubé, Marie-Pierre, additional, Thorin, Éric, additional, Ledoux, Jonathan, additional, Rhainds, David, additional, Rhéaume, Éric, additional, and Tardif, Jean-Claude, additional

Published
2022
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45. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Author

Cadrin-Tourigny, Julia, primary, Bosman, Laurens P, additional, Nozza, Anna, additional, Wang, Weijia, additional, Tadros, Rafik, additional, Bhonsale, Aditya, additional, Bourfiss, Mimount, additional, Fortier, Annik, additional, Lie, Øyvind H, additional, Saguner, Ardan M, additional, Svensson, Anneli, additional, Andorin, Antoine, additional, Tichnell, Crystal, additional, Murray, Brittney, additional, Zeppenfeld, Katja, additional, van den Berg, Maarten P, additional, Asselbergs, Folkert W, additional, Wilde, Arthur A M, additional, Krahn, Andrew D, additional, Talajic, Mario, additional, Rivard, Lena, additional, Chelko, Stephen, additional, Zimmerman, Stefan L, additional, Kamel, Ihab R, additional, Crosson, Jane E, additional, Judge, Daniel P, additional, Yap, Sing Chien, additional, van der Heijden, Jeroen F, additional, Tandri, Harikrishna, additional, Jongbloed, Jan D H, additional, Guertin, Marie Claude, additional, van Tintelen, J Peter, additional, Platonov, Pyotr G, additional, Duru, Firat, additional, Haugaa, Kristina H, additional, Khairy, Paul, additional, Hauer, Richard N W, additional, Calkins, Hugh, additional, te Riele, Anneline S J M, additional, and James, Cynthia A, additional

Published
2022
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47. Abstract

Author

Rasic, Nivez F., Friesen, Robert M., Anderson, Bruce, Hoban, Shirley A., Olson, Nancy, Kress, Jacob, Lévesque, Simon, Lessard, Martin R., Nicole, Pierre, Langevin, Stéphan, Langevin, Jacques, LeBlanc, François, Brochu, Jacques, Turgeon, Alexis, Nicole, Pierre C., Lessard, Martin R., Trépanier, Claude A., Marcoux, Sylvie, Lash, Vynka C., Anderson, Keith, Asenjo, J. Francisco, Carli, Francesco, Engen, Dale A., Morewood, Gordon H., Ghazar, Nancy, Ashbury, Ted, VanDenKerkhof, Elizabeth G., Wang, Louie, Blight, Katherine R., Mazer, C. David, Hare, Gregory M. T., Wang, Zhilan, Coackley, Carla, Qu, Rong, Robb, Malcolm, Stewart, Duncan J., Schricker, Thomas, Meterissian, Sarkis, Lattermann, Ralph, Carli, Franco, Dupuis, Jean-Yves, Wang, Feng, Nathan, Howard, Williams, Kathryn, Robblee, James A., Nathan, Howard J., Dupuis, Jean-Yves, Wang, Feng, Ko, Raynauld, Kruger, Marelise, McRae, Karen, Darling, Gail, Waddell, Thomas, Morrice, David, McGlade, Desmond, Cheung, Ken, Katz, Joel, Slinger, Peter, Hare, Gregory M. T., Baker, Andrew J., Hum, Kathryn M., Kim, Steve Y., Qu, Rong, Barr, Aiala, Mazer, C. David, Friedman, Zeev, Wong, David T., Chung, Frances, VanDenKerkhof, Elizabeth G., Goldstein, David H., Blaine, William C., Rimmer, Michael J., Kolman, Jacelyn M., Hung, Orlando R., Beauprie, Ian G., Vandorpe, Robert, Baker, Chandran J., Rennie, William, Brown, Robert, Kenny, Susan, Kamming, Damon, McGrath, Brid, Chung, Frances, Curti, Bruna, King, Shirley, Lau, Brenda W., Ries, Craig R., Schmid, Josie, Kraima, Richard N., Arai, Toshimi, Yamashita, Masao, Splinter, William, Parekh, Uma R., Valois-Gomez, Teresa, Muir, John G., Usher, Andrew G., Kearney, Ramona A., Tsui, Ban C. H., Shende, D., Darlong, V., Asit, N., Tsui, Ban C. H., Richards, Justin, Van Aerde, John, Tsui, Ban C. H., Tsui, Ban C. H., Wagner, Alese, Cave, Dominic, Kearney, Ramona, Philips, Leeanne, Reid, Kathy, Chowdary, Khalid, Splinter, William, Brooks, Peter, Ree, Ron, Ansermino, Mark, Rosen, David, Manninen, Pirjo H., Ghazaime, Ghazali, Louissi, Soad, Odukoya, Bisi, Nathan, Howard J., Rodriguez, Rosendo A., Dupuis, Jean-Yves, Parlea, Luciana, Rubens, Fraser D., Hendry, Paul, Lee, Il-Ok, Lee, In Ho, Audu, Paul, Mak, Peter H. K., Manninen, Pirijo H., Sundar, Shanti, Schwarz, Stephan K. W., Puil, Ernest, Hybarger, Steven E., Sloan, Tod B., Brull, Richard, McCartney, Colin J. L., Rawson, Regan, Abbas, Sherif, Chan, Vincent W. S., Ong, D., Ha, D., Ha, H., McKay, W. P. S., Lee, Il-Ok, Kong, Myung-Hoon, Lee, Mi-Kyung, Lim, Sang-Ho, Choi, Young-Seok, Kim, Nan-Sook, Lennox, P. H., Umedaly, H. S., Keogh, C. F., Setton, D., Grant, R. P., Fitzmaurice, B. G., Evans, K., Lennox, P. H., Umedaly, H. S., White, S. A., Grant, R. P., Fitzmaurice, B. G., Evans, K., Chan, Vincent W. S., Watt-Watson, Judy, Chung, Frances, McGillion, Michael, Daley, M. Denise, Normanaf], Peter H., Hogervorst, Sarah, Kowalski, Alicia, Arens, James, Kennamer, Debra, Curley, Steven, Vauthey, Jean, Tsui, Ban C. H., Wagner, Alese, Finucaneaf], Brendan, Beattie, W. Scott, Choi, Peter, Chowdary, Khalid, Splinter, William, Donais, Phillip E., McKay, William P. S., Banner, Robert, Kennedy, Renee, Konok, George, Guglielmin, Darryl R., King, Francis G., Hwang, Kyungil, Kim, Hoondo, Lee, Sangho, Cardinal, Valérie, Martin, René, Tétreault, Jean-Pierre, Colas, Marie-José, Gagnon, Linda, Claprood, Yves, Schricker, Thomas, Wykes, Linda, Carli, Franco, Luo, Tao, Xia, Zhengyuan, Ansley, David M., Ouyang, Jingping, Xia, Zhong-Yuan, Brousseau, Paul, Dobson, Greg, Lummis, Heather, Arellano, Ramiro, Steinberg, David, Trigazis, Leo, Devito, Isabella, Downey, Kristi, Minogue, Sean, Ralph, James, Lampa, Martin, Roscoe, Andrew J., Sawchuk, Corey W., Fayad, Ashraf, Healey, Jeff, Crystal, Eugene, Teoh, Kevin, Lonn, Eva, Carroll, Sandra, Hohnloser, Stephan, Connolly, Stuart, Rodriguez, Rosendo A., Lavallee, Gilbert, Rubens, Fraser, Nathan, Howard J., Rodriguez, Rosendo A., Rodriguez, Carlos D., Lavallee, Gilbert, Rubens, Fraser D., Nathan, Howard J., Robitaille, Arnaud, Denault, André Y., Couture, Pierre, Bélisle, Sylvain, Fortier, Annik, Guertin, Marie-Claude, Carrier, Michel, Martineau, Raymond, Basran, Sukhjeewan, Frumento, Robert, O’Malley, Catherine, Mongero, Linda, Beck, James, Bennett-Guerrero, Elliott, Hemmerling, Thomas M., Choinière, Jen-Luc, Basile, Fadi, Prieto, Ignatio, Fortier, Joanne D., MacAdams, Charles, Fan, Lawrence, Seal, Douglas, Maier, Karen, Kowalewski, Richard, Tang, Tim, Haigh, John, Tofflemire, Karen, Norris, James Q., Howells, Steven, Browne, Joseph, Beney, Andrew, Pynn, Todd, Taylor, Steven, Mong, Kam, Djaiani, George, Fedorko, Ludwik, Carroll, Jo, Ali, Mohamed, Cheng, Davy, Klein, Andrew, Rakowski, Harry, Woo, Anna, Heinrich, Lee, Mikulis, David, Karski, Jacek, Sia, Alex, Chua, Sebastian, Hong, Xi, Gvozdic, Branka, Schricker, Thomas, Carli, Franco, Morgan, Pamela J., Tarshis, Jordan, Macarthur, Alison J., Brant, Rollin, Pollard, Jeffrey, Cook, Linda, Yoon, Hea Jo, Lee, Youn Woo, Hong, Jeong-Yeon, Kim, Soo Mie, Parkhurst, Sherry, Biehl, Diane, Ong, Bill, Lessard, Martin R., Nicole, Pierre, Brochuaf], Jacques, Langevin, Stéphan, Croft, Dary, Ho, Anthony M. -H., Lee, Tak Wai, Karmakar, Manoj K., Lam, Wynnie M., Chung, David C., Massicotte, Luc, Wilkes, Peter R. H., Legault, Stephan, Gupta, Sanjiv, Baxter, Alan D., Allan, J. E., Tsui, Ban C. H., Malherbe, Stephan, Baxter, Alan D., Allan, J., Bedard, J., Malone-Tucker, S., Slivar, S., Langil, M., Perrault, M., Janseo, O., Carvalho, George, Moore, Anne, Lachapelle, Kevin, Quizilbash, Baqir, Schricker, Thomas, Salem, Reda, Denault, André Y., Couture, Pierre, Bélisle, Sylvain, Fortier, Annik, Guertin, Marie-Claude, Carrier, Michel, Martineau, Raymond, Klein, Andrew A., Djaiani, George, Shayan, Charles, Carroll, Jo, Chamchad, Dmitri, Fedorko, Ludwik, Cheng, Davy, Karski, Jacek, Keyvan, Karkouti, Bird, Sally J., Feldman, Liane S., Anidjar, Maurice, Stanbridge, Donna, Carli, Franco, Klein, Andrew, Karkouti, Keyvan, Abdelnaem, Esam, Wijeysundera, Duminda, Beattie, Scott, Yau, Terry, Sutton, David, Varadarajan, Bharathi, Klein, Andrew, Jose, Geraldine, Djaiani, George, Fedorko, Ludwik, Carroll, Jo, Karski, Jacek, Kakizawa, Karen, McCluskey, Stuart A., Karkouti, Keyvan, Ghannam, Mohammed, Smith, Robert, Goldman, Adam, Hsu, Janet, Abdelnaem, Esam, Duviner, Geoff, Sutton, David, Grant, David, Levy, Gary, Chamchad, Dmitri, Djaiani, George, Chang, Alvin, Karski, Jacek, Carroll, Jo, Shayan, Charles, Karkouti, Keyvan, Abdelnaem, Esam, Wijeysundera, Duminda, Borger, Michael, Djaiani, George, Ghannam, Mohammed, Morgan, Pamela J., Cleave-Hogg, Doreen, DeSousa, Susan, Tarshis, Jordan, Gvozdic, Branka, Hong, Xi, Schricker, Thomas, Carli, Franco, Radwan, Omar, Fried, Gerald, Carli, Franco, Gvozdic, Branka, Carli, Franco, Backman, Steven, Christou, Nicolas, Schricker, Thomas, Ghazar, Nancy, Morewood, Gordon H., Engen, Dale, Ashbury, Ted, VanDenKerkhof, Elizabeth G., Wang, Louie, Tarshis, Jordan, DeSousa, Susan, Brown, Russell, Iglesias, Stuart, Kohlhammer, Monica, Tanzola, Rob C., VanDenKerkhof, Elizabeth G., Milne, Brian, Doyle, D. John, Joo, Hwan, Frazer, Cassandra, Iacolucci, Anthony, Bagrin, Andrew, Small, Orville, Lewin, Warren, Chowet, Anne L., Lopez, Jaime R., Brock-Utne, John, Jaffe, Richard A., Milne, Andrew D., Muir, John G., Lee, J. Michael, English, Michael J. M., Hung, O. R., Tsui, Ban C. H., and Finucane, Brendan

Published
2003
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48. Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in atheroprotection.

Author

Rautureau, Yohann, Berlatie, Marianne, Rivas, Daniel, Uy, Kurunradeth, Blanchette, Alexandre, Miquel, Géraldine, Higgins, Marie-Ève, Mecteau, Mélanie, Nault, Audrey, Villeneuve, Louis, Lavoie, Véronique, Théberge-Julien, Gabriel, Brand, Geneviève, Lapointe, Line, Denis, Maxime, Rosa, Camille, Fortier, Annik, Blondeau, Lucie, Guertin, Marie-Claude, and Dubé, Marie-Pierre

Subjects
ADENYLATE cyclase, VASOACTIVE intestinal peptide, FEMORAL artery, ENDOTHELIAL cells, CYTOSKELETON
Abstract

Aims The adenylate cyclase type 9 (ADCY9) gene appears to determine atherosclerotic outcomes in patients treated with dalcetrapib. In mice, we recently demonstrated that Adcy9 inactivation potentiates endothelial function and inhibits atherogenesis. The objective of this study was to characterize the contribution of ADCY9 to the regulation of endothelial signalling pathways involved in atherosclerosis. Methods and results We show that ADCY9 is expressed in the endothelium of mouse aorta and femoral arteries. We demonstrate that ADCY9 inactivation in cultured endothelial cells paradoxically increases cAMP accumulation in response to the adenylate cyclase activators forskolin and vasoactive intestinal peptide (VIP). Reciprocally, ADCY9 overexpression decreases cAMP production. Using mouse femoral artery arteriography, we show that Adcy9 inactivation potentiates VIP-induced endothelial-dependent vasodilation. Moreover, Adcy9 inactivation reduces mouse atheroma endothelial permeability in different vascular beds. ADCY9 overexpression reduces forskolin-induced phosphorylation of Ser157-vasodilator-stimulated phosphoprotein (VASP) and worsens thrombin-induced fall of RAP1 activity, both leading to increased endothelial permeability. ADCY9 inactivation in thrombin-stimulated human coronary artery endothelial cells results in cAMP accumulation, increases p-Ser157-VASP, and inhibits endothelial permeability. MLC2 phosphorylation and actin stress fibre increases in response to thrombin were reduced by ADCY9 inactivation, suggesting actin cytoskeleton regulation. Finally, using the Miles assay, we demonstrate that Adcy9 regulates thrombin-induced endothelial permeability in vivo in normal and atherosclerotic animals. Conclusion Adcy9 is expressed in endothelial cells and regulates local cAMP and endothelial functions including permeability relevant to atherogenesis. [ABSTRACT FROM AUTHOR]

Published
2023
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