45 results on '"Monaco, Claudia"'
Search Results
2. Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis
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Kwok, Andrew J., Allcock, Alice, Ferreira, Ricardo C., Cano-Gamez, Eddie, Smee, Madeleine, Burnham, Katie L., Zurke, Yasemin-Xiomara, McKechnie, Stuart, Mentzer, Alexander J., Monaco, Claudia, Udalova, Irina A., Hinds, Charles J., Todd, John A., Davenport, Emma E., and Knight, Julian C.
- Abstract
Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n= 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils. In co-culture, CD66b+sepsis neutrophils inhibited proliferation and activation of CD4+T cells. Single-cell multiomic mapping of circulating hematopoietic stem and progenitor cells (HSPCs) (29,366 cells, n= 27) indicated altered granulopoiesis in patients with sepsis. These features were enriched in a patient subset with poor outcome and a specific sepsis response signature that displayed higher frequencies of IL1R2+immature neutrophils, epigenetic and transcriptomic signatures of emergency granulopoiesis in HSPCs and STAT3-mediated gene regulation across different infectious etiologies and syndromes. Our findings offer potential therapeutic targets and opportunities for stratified medicine in severe infection.
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- 2023
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3. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19
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Kotanidis, Christos P, Xie, Cheng, Alexander, Donna, Rodrigues, Jonathan C L, Burnham, Katie, Mentzer, Alexander, O’Connor, Daniel, Knight, Julian, Siddique, Muhammad, Lockstone, Helen, Thomas, Sheena, Kotronias, Rafail, Oikonomou, Evangelos K, Badi, Ileana, Lyasheva, Maria, Shirodaria, Cheerag, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Adlam, David, Rao, Praveen, Indrajeet, Das, Deshpande, Aparna, Bajaj, Amrita, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Ho, Ling-Pei, Neubauer, Stefan, Newby, David E, Channon, Keith M, Deanfield, John, Antoniades, Charalambos, 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, and Lin, Wen-Hua
- Abstract
Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19.
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- 2022
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4. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?
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Engelen, Suzanne E., Robinson, Alice J. B., Zurke, Yasemin-Xiomara, and Monaco, Claudia
- Abstract
Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the formation of plaques containing lipid, connective tissue and immune cells in the intima of large and medium-sized arteries. Over the past three decades, a substantial reduction in cardiovascular mortality has been achieved largely through LDL-cholesterol-lowering regimes and therapies targeting other traditional risk factors for cardiovascular disease, such as hypertension, smoking, diabetes mellitus and obesity. However, the overall benefits of targeting these risk factors have stagnated, and a huge global burden of cardiovascular disease remains. The indispensable role of immunological components in the establishment and chronicity of atherosclerosis has come to the forefront as a clinical target, with proof-of-principle studies demonstrating the benefit and challenges of targeting inflammation and the immune system in cardiovascular disease. In this Review, we provide an overview of the role of the immune system in atherosclerosis by discussing findings from preclinical research and clinical trials. We also identify important challenges that need to be addressed to advance the field and for successful clinical translation, including patient selection, identification of responders and non-responders to immunotherapies, implementation of patient immunophenotyping and potential surrogate end points for vascular inflammation. Finally, we provide strategic guidance for the translation of novel targets of immunotherapy into improvements in patient outcomes.
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- 2022
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5. The Potential for Repurposing Anti-TNF as a Therapy for the Treatment of COVID-19
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Robinson, Philip C., Liew, David F.L., Liew, Jean W., Monaco, Claudia, Richards, Duncan, Shivakumar, Senthuran, Tanner, Helen L., and Feldmann, Marc
- Abstract
Coronavirus disease 2019 (COVID-19) currently has few effective treatments. Given the uncertainty surrounding the effectiveness and uptake of a vaccine, it is important that the search for treatments continue. An exaggerated inflammatory state is likely responsible for much of the morbidity and mortality in COVID-19. Elevated levels of tumor necrosis factor (TNF), a key pro-inflammatory cytokine, have been shown to be associated with increased COVID-19 mortality. In patients with rheumatoid arthritis, TNF blockade reduces not only biologically active TNF but other pro-inflammatory cytokines important in COVID-19 hyperinflammation. Observational data from patients already on anti-TNF therapy show a reduced rate of COVID-19 poor outcomes and death compared with other immune-suppressing therapies. Anti-TNF has a long history of safe use, including in special at-risk populations, and is widely available. The case to adequately assess anti-TNF as a treatment for COVID-19 is compelling.
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- 2020
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6. Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91.
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Trauelsen, Mette, Rexen Ulven, Elisabeth, Hjorth, Siv A., Brvar, Matjaz, Monaco, Claudia, Frimurer, Thomas M., and Schwartz, Thue W.
- Abstract
Objective Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. Methods and results Here we first determined that the cis conformation of the succinate backbone is preferred and that certain backbone modifications are allowed for GPR91 activation. Through receptor modeling over the X-ray structure of the closely related P2Y1 receptor, we discovered that the binding pocket is partly occupied by a segment of an extracellular loop and that succinate therefore binds in a very different mode than generally believed. Importantly, an empty side-pocket is identified next to the succinate binding site. All this information formed the basis for a substructure-based search query, which, combined with molecular docking, was used in virtual screening of the ZINC database to pick two serial mini-libraries of a total of only 245 compounds from which sub-micromolar, selective GPR91 agonists of unique structures were identified. The best compounds were backbone-modified succinate analogs in which an amide-linked hydrophobic moiety docked into the side-pocket next to succinate as shown by both loss- and gain-of-function mutagenesis. These compounds displayed GPR91-dependent activity in altering cytokine expression in human M2 macrophages similar to succinate, and importantly were devoid of any effect on the major intracellular target, succinate dehydrogenase. Conclusions These novel, synthetic non-metabolite GPR91 agonists will be valuable both as pharmacological tools to delineate the GPR91-mediated functions of succinate and as leads for the development of GPR91-targeted drugs to potentially treat low grade metabolic inflammation and diabetic complications such as retinopathy and nephropathy. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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7. Interplay between hypercholesterolaemia and inflammation in atherosclerosis: Translating experimental targets into clinical practice
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Tuñón, José, Bäck, Magnus, Badimón, Lina, Bochaton-Piallat, Marie-Luce, Cariou, Bertrand, Daemen, Mat J, Egido, Jesus, Evans, Paul C, Francis, Sheila E, Ketelhuth, Daniel FJ, Lutgens, Esther, Matter, Christian M, Monaco, Claudia, Steffens, Sabine, Stroes, Erik, Vindis, Cécile, Weber, Christian, and Hoefer, Imo E
- Abstract
Dyslipidaemia and inflammation are closely interconnected in their contribution to atherosclerosis. In fact, low-density lipoprotein (LDL)-lowering drugs have anti-inflammatory effects. The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) has shown that interleukin (IL)-1β blockade reduces the incidence of cardiovascular events in patients with previous myocardial infarction and C-reactive protein levels >2 mg/L. These data confirm the connection between lipids and inflammation, as lipids activate the Nod-like receptor protein 3 inflammasome that leads to IL-1β activation. LDL-lowering drugs are the foundation of cardiovascular prevention. Now, the CANTOS trial demonstrates that combining them with IL-1β blockade further decreases the incidence of cardiovascular events. However, both therapies are not at the same level, given the large evidence showing that LDL-lowering drugs reduce cardiovascular risk as opposed to only one randomized trial of IL-1β blockade. In addition, IL-1β blockade has only been studied in patients with C-reactive protein >2 mg/L, while the benefit of LDL-lowering is not restricted to these patients. Also, lipid-lowering drugs are not harmful even at very low ranges of LDL, while anti-inflammatory therapies may confer a higher risk of developing fatal infections and sepsis. In the future, more clinical trials are needed to explore whether targeting other inflammatory molecules, both related and unrelated to the IL-1β pathway, reduces the cardiovascular risk. In this regard, the ongoing trials with methotrexate and colchicine may clarify whether the cardiovascular benefit of IL-1β blockade extends to other anti-inflammatory mechanisms. A positive result would represent a major change in the future treatment of atherosclerosis.
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- 2018
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8. Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis
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Seneviratne, Anusha N., Edsfeldt, Andreas, Cole, Jennifer E., Kassiteridi, Christina, Swart, Maarten, Park, Inhye, Green, Patricia, Khoyratty, Tariq, Saliba, David, Goddard, Michael E., Sansom, Stephen N., Goncalves, Isabel, Krams, Rob, Udalova, Irina A., and Monaco, Claudia
- Abstract
Supplemental Digital Content is available in the text.
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- 2017
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9. Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques
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Shalhoub, Joseph, Viiri, Leena E., Cross, Amanda J., Gregan, Scott M., Allin, David M., Astola, Nagore, Franklin, Ian J., Davies, Alun H., and Monaco, Claudia
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- 2016
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10. Role and analysis of monocyte subsets in cardiovascular disease
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Weber, Christian, Shantsila, Eduard, Hristov, Michael, Caligiuri, Giuseppina, Guzik, Tomasz, Heine, Gunnar H., Hoefer, Imo E., Monaco, Claudia, Peter, Karlheinz, Rainger, Ed, Siegbahn, Agneta, Steffens, Sabine, Wojta, Johann, and Lip, Gregory Y. H.
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- 2016
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11. B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10
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Strom, Asa C., Cross, Amanda J., Cole, Jennifer E., Blair, Paul A., Leib, Christoph, Goddard, Michael E., Rosser, Elizabeth C., Park, Inhye, Nilsson, Anna Hultgårdh, Nilsson, Jan, Mauri, Claudia, and Monaco, Claudia
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- 2015
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12. Macrophages and Dendritic Cells: The Usual Suspects in Atherogenesis
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Kassiteridi, Christina and Monaco, Claudia
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Atherosclerosis, the major risk factor for cardiovascular disease (CVD) and the leading cause of death worldwide, is a multifactorial chronic inflammatory disease, which, clinically manifests from early lipid-rich lesions to plaque rupture and/or thrombosis in the arterial wall. The myeloid cell compartment, including macrophages and dendritic cells (DCs), is long known to contribute to the initiation and progression of atherosclerosis. However their complex phenotypic heterogeneity hampers our full understanding of their role. Here, we review the biological and functional versatility of the myeloid cells in atherosclerosis. Several distinct subsets of macrophages and myeloid cells have been identified in atherosclerotic plaques, including subsets that are specific to atherosclerosis itself. Our ability to target them therapeutically is still limited. The challenge for the future will be the definition of treatments that target specific myeloid subsets to prevent the activation of pro-atherogenic myeloid cell subsets while preserving the anti-atherogenic and repairable function of myeloid cells.
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- 2015
13. Anti-apoA-1 auto-antibodies increase mouse atherosclerotic plaque vulnerability, myocardial necrosis and mortality triggering TLR2 and TLR4
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Montecucco, Fabrizio, Braunersreuther, Vincent, Burger, Fabienne, Lenglet, Sébastien, Pelli, Graziano, Carbone, Federico, Fraga-Silva, Rodrigo, Stergiopulos, Nikolaos, Monaco, Claudia, Mueller, Christian, Pagano, Sabrina, Dallegri, Franco, Mach, François, and Vuilleumier, Nicolas
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- 2015
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14. Role of Inflammatory Cells and Toll-Like Receptors in Atherosclerosis
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N. Seneviratne, Anusha and Monaco, Claudia
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The primary cause of cerebrovascular disease is atherosclerosis, to which many factors contribute. At first many saw atherosclerosis as a lipid-driven disease. Recently inflammation has appeared as a significant factor in the disease. Innate immune cells, for example monocytes and macrophages, are important in atherosclerosis. Toll-like receptors (TLRs) are the best-studied family of receptor in the immune system. TLR engagement with their ligands stimulates pro-inflammatory cytokine production and foam cell generation. Recently certain TLRs have shown a protective role in atherosclerosis. In this review, we analyse innate immunity, focusing on TLR signalling and macrophages, in atherosclerosis and acute cerebrovascular complications, and thereby discuss their potential as therapeutic targets.
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- 2015
15. Comparative Lipidomics Profiling of Human Atherosclerotic Plaques.
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Stegemann, Christin, Drozdov, Ignat, Shalhoub, Joseph, Humphries, Julia, Ladroue, Christophe, Didangelos, Athanasios, Baumert, Mark, Allen, Mark, Davies, Alun H., Monaco, Claudia, Smith, Alberto, Qingbo Xu, and Mayr, Manuel
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MASS spectrometry ,LIPIDS ,RADIAL artery ,ENDARTERECTOMY ,ATHEROSCLEROTIC plaque - Abstract
The article discusses a study on the latest mass spectrometry (MS) developments in shotgun lipidomics which compared radial arteries, endarterectomy samples from symptomatic and asymptomatic patients and stable and unstable areas within the same symptomatic lesion. Twenty six patients were included in the study and the control radial arteries were carefully chosen. It refers to the study as the most comprehensive MS analysis of the lipid content in human atherosclerotic plaques to date.
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- 2011
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16. Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.
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Ikonomidis, Ignatios, Athanassopoulos, George, Stamatelopoulos, Kimon, Lekakis, John, Revela, Ioanna, Venetsanou, Kiriaki, Marinou, Margarita, Monaco, Claudia, Cokkinos, Dennis V., and Nihoyannopoulos, Petros
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INTERLEUKIN-6 ,DOBUTAMINE ,ECHOCARDIOGRAPHY ,CORONARY disease ,CARDIAC catheterization ,INTERLEUKINS ,LONGITUDINAL method ,MULTIVARIATE analysis ,PROGNOSIS ,THROMBOPLASTIN ,PROPORTIONAL hazards models ,RECEIVER operating characteristic curves ,KAPLAN-Meier estimator ,DIAGNOSIS - Abstract
Background: Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD).Methods: We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated.Results: Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P < .01 for an adverse event). The addition of peak wall motion score index in a multivariable model including risk factors, ejection fraction, revascularization, and multivessel disease increased the model's c statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events.Conclusions: Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD. [ABSTRACT FROM AUTHOR]- Published
- 2008
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17. Toll-Like Receptor 7 Protects From Atherosclerosis by Constraining “Inflammatory” Macrophage Activation
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Salagianni, Maria, Galani, Ioanna E., Lundberg, Anna M., Davos, Constantinos H., Varela, Aimilia, Gavriil, Ariana, Lyytikäinen, Leo-Pekka, Lehtimäki, Terho, Sigala, Fragiska, Folkersen, Lasse, Gorgoulis, Vassilis, Lenglet, Sébastien, Montecucco, Fabrizio, Mach, François, Hedin, Ulf, Hansson, Göran K., Monaco, Claudia, and Andreakos, Evangelos
- Abstract
Toll-like receptors (TLRs) have long been considered to be major culprits in the development of atherosclerosis, contributing both to its progression and clinical complications. However, evidence for most TLRs beyond TLR2 and TLR4 is lacking.
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- 2012
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18. The Tolls and Dangers of Atherosclerotic Disease
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Monaco, Claudia
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Inflammation drives atherosclerosis. Toll-like receptor-2 and -4 are so far the strongest candidates for initiating innate immune signalling in atherosclerosis. Their signalling has implications for lesion development, foam cell formation, inflammation, matrix degradation and ischemia-reperfusion. The repertoire of TLR agonists is expanding. They collectively represent a conglomerate of structurally diverse molecular patterns requiring a high level of versatility in their sensing. Such versatility is achieved through cooperation of TLR heterodimers, co-receptors, and binding proteins. Several endogenous and exogenous molecular patterns engaging TLRs are associated with atherosclerosis development and complications. In this review, I describe how such molecular patterns are sensed, how they signal and what the consequences in the atherosclerotic plaque might be. The effect of TLR antagonising compounds in human and murine atherosclerosis is also addressed.
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- 2012
19. Targeting Inflammation as a Therapeutic Strategy in Accelerated Atherosclerosis in Rheumatoid Arthritis
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Full, Louise E. and Monaco, Claudia
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Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population. Patients have reduced life expectancy and the leading cause of death is cardiovascular disease (CVD), with patients experiencing at least a 2‐fold increased risk of myocardial infarction. RA is recognized as an independent risk factor for CVD. Inflammation is a key contributor to the pathogenesis of atherosclerosis and cardiovascular events. As a common catalyst of both diseases, inflammation is the likely cause of increased prevalence of CVD in the RA population. Abating disease‐related inflammation in RA may be an effective strategy in reducing CVD risk. Several other therapies used to modify cardiovascular risk factors in the general population such as statins and angiotensin‐converting enzyme inhibitors are under investigation in patients with RA. This review discusses the parallels in the pathology of RA and atherosclerosis and discusses current therapies for RA and how they affect cardiovascular risk.
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- 2011
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20. Comparative Lipidomics Profiling of Human Atherosclerotic Plaques
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Stegemann, Christin, Drozdov, Ignat, Shalhoub, Joseph, Humphries, Julia, Ladroue, Christophe, Didangelos, Athanasios, Baumert, Mark, Allen, Mark, Davies, Alun H., Monaco, Claudia, Smith, Alberto, Xu, Qingbo, and Mayr, Manuel
- Abstract
We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques.
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- 2011
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21. Toll‐like receptor signaling: Common pathways that drive cardiovascular disease and rheumatoid arthritis
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Monaco, Claudia, Terrando, Niccolo, and Midwood, Kim S.
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- 2011
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22. Echocardiographic identification of the oblique vein of the left atrium: its relationship to the persistent left superior caval vein
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Linhares, Renata R., Suaide Silva, Carlos E., Monaco, Claudia G., Ferreira, Luiz D. Cortez, Gil, Manuel A., Ortiz, Juarez, Anderson, Robert H., and Aiello, Vera D.
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AbstractThus far, little has been written concerning echocardiographic identification of the oblique vein of the left atrium, or Marshall?s vein. There is much discussion, nonetheless, on the potential significance of the vein, or its ligamentous remnant, as an arrhythmic substrate. We describe here four patients in whom transthoracic echocardiography revealed a venous structure protruding within the cavity of the left atrium. We discuss the possibility that these structures represent Marshall?s vein, albeit probably as part of a persistent left superior caval vein.
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- 2010
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23. The inextricable link between atherosclerosis and prototypical inflammatory diseases rheumatoid arthritis and systemic lupus erythematosus
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Full, Louise, Ruisanchez, Cristina, and Monaco, Claudia
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The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has recently become the focus of intense investigation. Proatherogenic risk factors and dysregulated inflammation are the main culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways shared by atherosclerosis and inflammatory disease may be involved. In this review we map the key determinants of the increased incidence of cardiovascular disease in patients with inflammatory diseases at each step of the atherogenesis.
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- 2009
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24. C‐reactive protein (CRP) induces chemokine secretion via CD11b/ICAM‐1 interaction in human adherent monocytes
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Montecucco, Fabrizio, Steffens, Sabine, Burger, Fabienne, Pelli, Graziano, Monaco, Claudia, and Mach, François
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Several studies support C‐reactive protein (CRP) as a systemic cardiovascular risk factor. The recent detection of CRP in arterial intima suggests a dual activity in atherosclerosis as a circulating and tissue mediator on vascular and immune cells. In the present paper, we focused on the inflammatory effects of CRP on human monocytes, which were isolated by Ficoll‐Percoll gradients and cultured in adherence to polystyrene, endothelial cell monolayer, or in suspension. Chemokine levels, adhesion molecule, and chemokine receptor expression were detected by ELISA, flow cytometry, and real‐time RT‐PCR. Migration assays were performed in a Boyden chamber. Stimulation with CRP induced release of CCL2, CCL3, and CCL4 in adherent monocytes through the binding to CD32a, CD32b, and CD64, whereas no effect was observed in suspension culture. This was associated with CRP‐induced up‐regulation of adhesion molecules membrane‐activated complex 1 (Mac‐1) and ICAM‐1 on adherent monocytes. Blockade of Mac‐1/ICAM‐1 interaction inhibited the CRP‐induced chemokine secretion. In addition, CRP reduced mRNA and surface expression of corresponding chemokine receptors CCR1, CCR2, and CCR5 in adherent monocytes. This effect was a result of chemokine secretion, as coincubation with neutralizing anti‐CCL2, anti‐CCL3, and anti‐CCL4 antibodies reversed the effect of CRP. Accordingly, a reduced migration of CRP‐treated monocytes to CCL2 and CCL3 was observed. In conclusion, our data suggest an in vitro model to study CRP activities in adherent and suspension human monocytes. CRP‐mediated induction of adhesion molecules and a decrease of chemokine receptors on adherent monocytes might contribute to the retention of monocytes within atherosclerotic lesions and recruitment of other circulating cells.
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- 2008
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25. Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems
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Lundberg, Anna M., Drexler, Stefan K., Monaco, Claudia, Williams, Lynn M., Sacre, Sandra M., Feldmann, Marc, and Foxwell, Brian M.
- Abstract
TLR3 recognizes double-stranded RNA, a product associated with viral infections. Many details of TLR3-induced mechanisms have emerged from gene-targeted mice or inhibition studies in transformed cell lines. However, the pathways activated in human immune cells or cells from disease tissue are less well understood. We have investigated TLR3-induced mechanisms of human primary cells of the innate immune system, including dendritic cells (DCs), macrophages (MØs), endothelial cells (ECs), and synovial fibroblasts isolated from rheumatoid arthritis joint tissue (RA-SFs). Here, we report that while these cells all express TLR3, they differ substantially in their response to TLR3 stimulation. The key antiviral response chemokine IP-10 was produced by all cell types, while DCs and MØs failed to produce the proinflammatory cytokines TNFα and IL-6. Unexpectedly, TNFα was found secreted by TLR3-stimulated RA-SF. Furthermore, TLR3 stimulation did not activate NFκB, MAPKs, or IRF-3 in DCs and MØs, but was able to do so in ECs and RA-SF. These findings were specific for human cells, thereby revealing a complexity not previously expected. This is the first report of such cell type– and species-specific response for any TLR stimulation and helps to explain important difficulties in correlating murine models of inflammatory diseases and human inflammation.
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- 2007
- Full Text
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26. Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems
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Lundberg, Anna M., Drexler, Stefan K., Monaco, Claudia, Williams, Lynn M., Sacre, Sandra M., Feldmann, Marc, and Foxwell, Brian M.
- Abstract
TLR3 recognizes double-stranded RNA, a product associated with viral infections. Many details of TLR3-induced mechanisms have emerged from gene-targeted mice or inhibition studies in transformed cell lines. However, the pathways activated in human immune cells or cells from disease tissue are less well understood. We have investigated TLR3-induced mechanisms of human primary cells of the innate immune system, including dendritic cells (DCs), macrophages (MØs), endothelial cells (ECs), and synovial fibroblasts isolated from rheumatoid arthritis joint tissue (RA-SFs). Here, we report that while these cells all express TLR3, they differ substantially in their response to TLR3 stimulation. The key antiviral response chemokine IP-10 was produced by all cell types, while DCs and MØs failed to produce the proinflammatory cytokines TNFα and IL-6. Unexpectedly, TNFα was found secreted by TLR3-stimulated RA-SF. Furthermore, TLR3 stimulation did not activate NFκB, MAPKs, or IRF-3 in DCs and MØs, but was able to do so in ECs and RA-SF. These findings were specific for human cells, thereby revealing a complexity not previously expected. This is the first report of such cell type– and species-specific response for any TLR stimulation and helps to explain important difficulties in correlating murine models of inflammatory diseases and human inflammation.
- Published
- 2007
- Full Text
- View/download PDF
27. TCRζdimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues
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Zhang, Zhuoli, Gorman, Claire L., Vermi, Anna-Chiara, Monaco, Claudia, Foey, Andrew, Owen, Sally, Amjadi, Parisa, Vallance, Alena, McClinton, Catherine, Marelli-Berg, Federica, Isomäki, Pia, Russell, Andrew, Dazzi, Francesco, Vyse, Timothy J., Brennan, Fionula M., and Cope, Andrew P.
- Abstract
The T-cell receptor ζ (TCRζ) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRζ expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRζ expression and effector function in T cells. We report here that TCRζdimlymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRζbrightcounterparts, TCRζdimcells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRζdimT cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRζdimT cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRζdimT cells make them promising cellular targets for the treatment of chronic inflammatory disease.
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- 2007
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28. TCRζdimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues
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Zhang, Zhuoli, Gorman, Claire L., Vermi, Anna-Chiara, Monaco, Claudia, Foey, Andrew, Owen, Sally, Amjadi, Parisa, Vallance, Alena, McClinton, Catherine, Marelli-Berg, Federica, Isomäki, Pia, Russell, Andrew, Dazzi, Francesco, Vyse, Timothy J., Brennan, Fionula M., and Cope, Andrew P.
- Abstract
The T-cell receptor ζ (TCRζ) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRζ expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRζ expression and effector function in T cells. We report here that TCRζdim lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRζbright counterparts, TCRζdim cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRζdim T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRζdim T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRζdim T cells make them promising cellular targets for the treatment of chronic inflammatory disease.
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- 2007
- Full Text
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29. Distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP
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Andreakos, Evangelos, Sacre, Sandra M., Smith, Clive, Lundberg, Anna, Kiriakidis, Serafim, Stonehouse, Tim, Monaco, Claudia, Feldmann, Marc, and Foxwell, Brian M.
- Abstract
How lipopolysaccharide (LPS) signals through toll-like receptors (TLRs) to induce nuclear factor (NF)–κB and inflammatory cytokines in sepsis remains unclear. Major candidates for that process are myeloid differentiation protein 88 (MyD88) and MyD88 adaptor-like/TIR domain-containing adaptor protein (Mal/TIRAP) but their role needs to be further defined. Here, we have examined the role of MyD88 and Mal/TIRAP in primary human cells of nonmyeloid and myeloid origin as physiologically relevant systems. We found that MyD88 and Mal/TIRAP are essential for LPS-induced IκBα phosphorylation, NF-κB activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. In contrast, in macrophages neither MyD88, Mal/TIRAP, nor IκB kinase 2 (IKK2) are required for NF-κB activation or tumor necrosis factor α (TNFα), IL-6, or IL-8 production, although Mal/TIRAP is still involved in the production of interferon β (IFNβ). Differential usage of TLRs may account for that, as in macrophages but not fibroblasts or endothelial cells, TLR4 is expressed in high levels at the cell surface, and neutralization of TLR4 but not TLR2 blocks LPS signaling. These observations demonstrate for the first time the existence of 2 distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of TLR4, MyD88, Mal/TIRAP, and IKK2, and reveal a layer of complexity not previously expected.
- Published
- 2004
- Full Text
- View/download PDF
30. Distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP
- Author
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Andreakos, Evangelos, Sacre, Sandra M., Smith, Clive, Lundberg, Anna, Kiriakidis, Serafim, Stonehouse, Tim, Monaco, Claudia, Feldmann, Marc, and Foxwell, Brian M.
- Abstract
How lipopolysaccharide (LPS) signals through toll-like receptors (TLRs) to induce nuclear factor (NF)–κB and inflammatory cytokines in sepsis remains unclear. Major candidates for that process are myeloid differentiation protein 88 (MyD88) and MyD88 adaptor-like/TIR domain-containing adaptor protein (Mal/TIRAP) but their role needs to be further defined. Here, we have examined the role of MyD88 and Mal/TIRAP in primary human cells of nonmyeloid and myeloid origin as physiologically relevant systems. We found that MyD88 and Mal/TIRAP are essential for LPS-induced IκBα phosphorylation, NF-κB activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. In contrast, in macrophages neither MyD88, Mal/TIRAP, nor IκB kinase 2 (IKK2) are required for NF-κB activation or tumor necrosis factor α (TNFα), IL-6, or IL-8 production, although Mal/TIRAP is still involved in the production of interferon β (IFNβ). Differential usage of TLRs may account for that, as in macrophages but not fibroblasts or endothelial cells, TLR4 is expressed in high levels at the cell surface, and neutralization of TLR4 but not TLR2 blocks LPS signaling. These observations demonstrate for the first time the existence of 2 distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of TLR4, MyD88, Mal/TIRAP, and IKK2, and reveal a layer of complexity not previously expected.
- Published
- 2004
- Full Text
- View/download PDF
31. T-Cell-Mediated Signalling in Immune, Inflammatory and Angiogenic Processes: The Cascade of Events Leading to Inflammatory Diseases
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Monaco, Claudia, Andreakos, Evangelos, Kiriakidis, Serafim, Feldmann, Marc, and Paleolog, Ewa
- Abstract
In the last decade, the understanding of the molecular mechanisms of regulation of the inflammatory process in chronic inflammatory diseases has moved remarkably forward. Recent evidence in various fields has consistently indicated that Tcells play a key role in initiating and perpetuating inflammation, not only via the production of soluble mediators but also via cell / cell contact interactions with a variety of cell types through membrane receptors and their ligands. Signalling through CD40 and CD40 ligand is a versatile pathway that is potently involved in all these processes. In this article, we review how T-cells become activated by dendritic cells or inflammatory cytokines, and how these T-cells activate, in turn, monocytes / macrophages, endothelial cells, smooth muscle cells and fibroblasts to produce pro-inflammatory cytokines (tumour necrosis factor α, interleukin-6), chemokines (interleukin-8, monocyte chemotactic protein-1), tissue factor, the main initiator of the coagulation cascade in vivo, and finally matrix metalloproteinases, responsible for tissue destruction. Moreover, we discuss how CD40 ligand at inflammatory sites stimulates fibroblasts and tissue monocyte / macrophage production of VEGF, leading to angiogenesis, which promotes and maintains the chronic inflammatory process. This cascade of events is discussed in the context of disease initiation / progression, with particular reference to atherosclerosis and rheumatoid arthritis, and to potential novel therapeutic targets for their treatment.
- Published
- 2004
32. IκB kinase 2 but not NF-κB–inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction
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Andreakos, Evangelos, Smith, Clive, Monaco, Claudia, Brennan, Fionula M., Foxwell, Brian M., and Feldmann, Marc
- Abstract
Although dendritic cells (DCs) are the most potent antigen-presenting cells involved in numerous physiologic and pathologic processes, little is known about the signaling pathways that regulate DC activation and antigen-presenting function. Recently, we demonstrated that nuclear factor (NF)-κB activation is central to that process, as overexpression of IκBα blocks the allogeneic mixed lymphocyte reaction (MLR), an in vitro model of T-cell activation. In this study, we investigated the role of 2 putative NF-κB–inducing components, NF-κB–inducing kinase (NIK), and IκB kinase 2 (IKK2). Using an adenoviral gene transfer method to efficiently express dominant-negative (dn) forms of these molecules in monocyte-derived DCs, we found that IKK2dn but not NIKdn inhibited the allogeneic MLR. When DCs were fixed, this inhibitory effect of IKK2dn was lost, suggesting that IKK2 is involved in T-cell–derived signals that enhance DC antigen presentation during the allogeneic MLR period and does not have an effect on viability or differentiation state of DCs prior to coculture with T cells. One such signal is likely to be CD40 ligand (CD40L), as IKK2dn blocked CD40L but not lipopolysaccharide (LPS)–induced NF-κB activation, cytokine production, and up-regulation of costimulatory molecules and HLA-DR in DCs. In summary, our results demonstrate that IKK2 is essential for DC activation induced by CD40L or contact with allogeneic T cells, but not by LPS, whereas NIK is not required for any of these signals. In addition, our results support IKK2 as a potential therapeutic target for the down-regulation of unwanted immune responses that may occur during transplantation or autoimmunity.
- Published
- 2003
- Full Text
- View/download PDF
33. IκB kinase 2 but not NF-κB–inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction
- Author
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Andreakos, Evangelos, Smith, Clive, Monaco, Claudia, Brennan, Fionula M., Foxwell, Brian M., and Feldmann, Marc
- Abstract
Although dendritic cells (DCs) are the most potent antigen-presenting cells involved in numerous physiologic and pathologic processes, little is known about the signaling pathways that regulate DC activation and antigen-presenting function. Recently, we demonstrated that nuclear factor (NF)-κB activation is central to that process, as overexpression of IκBα blocks the allogeneic mixed lymphocyte reaction (MLR), an in vitro model of T-cell activation. In this study, we investigated the role of 2 putative NF-κB–inducing components, NF-κB–inducing kinase (NIK), and IκB kinase 2 (IKK2). Using an adenoviral gene transfer method to efficiently express dominant-negative (dn) forms of these molecules in monocyte-derived DCs, we found that IKK2dn but not NIKdn inhibited the allogeneic MLR. When DCs were fixed, this inhibitory effect of IKK2dn was lost, suggesting that IKK2 is involved in T-cell–derived signals that enhance DC antigen presentation during the allogeneic MLR period and does not have an effect on viability or differentiation state of DCs prior to coculture with T cells. One such signal is likely to be CD40 ligand (CD40L), as IKK2dn blocked CD40L but not lipopolysaccharide (LPS)–induced NF-κB activation, cytokine production, and up-regulation of costimulatory molecules and HLA-DR in DCs. In summary, our results demonstrate that IKK2 is essential for DC activation induced by CD40L or contact with allogeneic T cells, but not by LPS, whereas NIK is not required for any of these signals. In addition, our results support IKK2 as a potential therapeutic target for the down-regulation of unwanted immune responses that may occur during transplantation or autoimmunity.
- Published
- 2003
- Full Text
- View/download PDF
34. T cell‐mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor
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Monaco, Claudia, Andreakos, Evangelos, Young, Sylvia, Feldmann, Marc, and Paleolog, Ewa
- Abstract
Adhesion of leukocytes to the vascular endothelium is an early event in inflammation. Since cell‐cell signaling may be an important stimulus for endothelial activation, we focused in this study on the role of contact‐mediated activation by T lymphocytes of endothelial cells (EC). T lymphocytes were cultured with anti‐CD3 monoclonal antibody or in the presence of a combination of TNF‐α, interleukin (IL)‐6, and IL‐2, prior to fixation and coculture with human umbilical vein EC. Fixed, activated (anti‐CD3‐ or cytokine‐stimulated), but not unstimulated T cells, induced release of monocyte chemotactic protein‐1, IL‐8, and IL‐6 by EC in a contact‐dependent manner. Moreover, expression of tissue‐factor antigen and activity was also significantly increased. Addition of anti‐CD40 ligand antibody abolished T cell‐induced activation of EC. Our data suggest that contact‐mediated activation of EC by T cells, involving ligand:counter ligand interactions such as CD40:CD40 ligand, may represent a novel pathogenic mechanism of progression in inflammatory diseases such as atherosclerosis or rheumatoid arthritis.
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- 2002
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35. Late-Phase Contrast-Enhanced Ultrasound Reflects Biological Features of Instability in Human Carotid Atherosclerosis.
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Shalhoub, Joseph, Monaco, Claudia, Owen, David R. J., Gauthier, Thomas, Thapar, Ankur, Leen, Edward L. S., and Davies, Alun H.
- Published
- 2011
- Full Text
- View/download PDF
36. Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction, but its reduction is not related to ischemia
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Biasucci, Luigi M., D'Onofrio, Giuseppe, Liuzzo, Giovanna, Zini, Gina, Monaco, Claudia, Caligiuri, Giuseppina, Tommasi, Maria, Rebuzzi, Antonio G., and Maseri, Attilio
- Abstract
Objectives. This study sought to assess neutrophil activation in acute coronary syndromes and its relation to ischemic episodes.
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- 1996
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- View/download PDF
37. COST-EFFECTIVE PHARMACOLOGICAL PREVENTION OF ACUTE CORONARY SYNDROMES
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MONACO, CLAUDIA, CIANFLONE, DOMENICO, SUMMARIA, FRANCESCO, MASERI, ATTILIO, and CREA, FILIPPO
- Abstract
The growing size of trials on primary and secondary prevention of acute coronary syndromes characterised by very broad inclusion criteria may seem logical to `trialists', who reason that the broader the inclusion criteria, the easier it is to recruit large numbers of patients in a short period of time and the more widely applicable are the results of the study. However, large trials with very broad inclusion criteria raise two grounds for concern for physicians. The first is that the broader the inclusion criteria for enrolment in a trial in order to prove a statistically significant benefit, the greater the heterogeneity of the study population which is likely to include both susceptible and non-susceptible patients to the tested treatment. The second is that this method of assessment rapidly increases the number of treatments that produce a statistically-significant improvement in prognosis within the same broad group of patients. On the contrary, the identification of potential responders to a specific treatment can provide a personalised form of medical care suited to the needs of each individual patient with an optimal cost–benefit ratio. This approach, however, represents a major challenge as it can only be based on the identification of homogeneous subgroups of patients with common risk factors for the development of acute coronary syndromes or of their recurrence. This challenge can only be overcome by a strong commitment in funding studies on the multiple causes of acute coronary syndromes.
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- 1998
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- View/download PDF
38. Late-Phase Contrast-Enhanced Ultrasound Reflects Biological Features of Instability in Human Carotid Atherosclerosis
- Author
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Shalhoub, Joseph, Monaco, Claudia, Owen, David R.J., Gauthier, Thomas, Thapar, Ankur, Leen, Edward L.S., and Davies, Alun H.
- Abstract
Development of translational functional imaging modalities for atherosclerosis risk stratification is sought for stroke prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP-CEUS) to quantify microbubble contrast retention within carotid atherosclerosis and shown it to separate asymptomatic plaques from those responsible for recent cerebrovascular events. We hypothesized that microbubbles are retained in areas of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque biology.
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- 2011
- Full Text
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39. False Tendon Connecting the Anterior Mitral Valve Leaflet to the Roof of the Left Atrium
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Silva, Carlos Eduardo Suaide, Peixoto, Luciana Braz, Monaco, Claudia G., Ferreira, Luiz Darcy C., Gil, Manuel Adán, Becker, Anton E., and Ortiz, Juarez
- Published
- 2002
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40. 973-113 Elevated C-Reactive Protein at Discharge and at Three Months After Waning of Symptoms in Unstable Angina is Associated with Recurrence of Instability During 12 Months Follow-up
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Liuzza, Giovanna, Biasucci, Luigi M., Buffon, Antonino, Quaranta, Gaetano, Caligiuri, Giuseppina, Monaco, Claudia, Grillo, Rita L., Rebuzzi, Antonio G., and Maseri, Attilio
- Abstract
We have previously reported that elevated levels of an acute phase reactant. C-Reactive Protein (CRP), are common in pts with unstable angina (UA) and related to short term outcome. To assess whether the increase of CRP in UA is a transient condition or persists after clinical stabilization, and whether elevated levels of CRP after stabilization are still associated with prognosis, we measured CRP in 34 patients (pts) with UA: blood samples were taken at discharge from the hospital and 3 months (3M) after the index event (during a stable phase of the disease). Clinical follow-up of all pts was performed for 12 months.
- Published
- 1995
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41. Plasminogen activation in unstable angina is associated with an acute phase response but not with activation of the hemostastic system
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Biasucci, Luigi M., Liuzzo, Giovanna, Quaranta, Gaetano, Massa, Laura, Caligluri, Giuseppina, Monaco, Claudia, Summaria, Francesco, van de Greef, Willy, Rebuzzi, Antonio G., Kluft, Cornelis, and Maseri, Attilio
- Published
- 1996
- Full Text
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42. Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow
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Caro, Colin Gerald, Seneviratne, Anusha, Heraty, Kevin B., Monaco, Claudia, Burke, Martin G., Krams, Rob, Chang, Carlos C., Gilson, Paul, and Coppola, Gianfilippo
- Published
- 2014
- Full Text
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43. Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow†
- Author
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Caro, Colin Gerald, Seneviratne, Anusha, Heraty, Kevin B., Monaco, Claudia, Burke, Martin G., Krams, Rob, Chang, Carlos C., Coppola, Gianfilippo, and Gilson, Paul
- Abstract
Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels.
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- 2013
- Full Text
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44. The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction
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Terrando, Niccolò, Rei Fidalgo, António, Vizcaychipi, Marcela, Cibelli, Mario, Ma, Daqing, Monaco, Claudia, Feldmann, Marc, and Maze, Mervyn
- Abstract
The impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide (LPS) challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 (HMGB-1), microglial activation, and cognitive dysfunction. Disabling the interleukin (IL)-1 signaling pathway is sufficient to reduce inflammation and ameliorate the disability.
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- 2010
- Full Text
- View/download PDF
45. 810-1 Enhanced Inflammatory Acute Phase Response After Percutaneous Coronary Angioplasty in Patients with Unstable Angina
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Liuzzo, Giovanna, Buffon, Antonino, Biasucci, Luigi M., De Felice, Francesco, Caligiuri, Giuseppina, Grillo, Rita L., Quaranta, Gaetano, Monaco, Claudia, Crea, Filippo, and Maseri, Attilio
- Abstract
Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, are independent predictors of short-term prognosis in patients (pts) with unstable angina (UA). The causes of the acute phase response in UA, however, are still unknown. Percutaneous transluminal coronary angioplasty (PTCA) is an useful model for the assessment of the effects of plaque disruption and myocardial ischemia on the acute phase response. Serum levels of CRP were measured in 21 pts with chronic stable angina (SA) (G 1) and in 22 pts with UA refractory to maximal medical treatment (G2), undergoing single-vessel PTCA. Venous blood samples were taken immediately before PTCA and 6, 24, 48, 72 hours after the end of the procedure. CRP values are expressed as median and range.
- Published
- 1995
- Full Text
- View/download PDF
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