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1. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author

Petros Andrikopoulos, Judith Aron-Wisnewsky, Rima Chakaroun, Antonis Myridakis, Sofia K. Forslund, Trine Nielsen, Solia Adriouch, Bridget Holmes, Julien Chilloux, Sara Vieira-Silva, Gwen Falony, Joe-Elie Salem, Fabrizio Andreelli, Eugeni Belda, Julius Kieswich, Kanta Chechi, Francesc Puig-Castellvi, Mickael Chevalier, Emmanuelle Le Chatelier, Michael T. Olanipekun, Lesley Hoyles, Renato Alves, Gerard Helft, Richard Isnard, Lars Køber, Luis Pedro Coelho, Christine Rouault, Dominique Gauguier, Jens Peter Gøtze, Edi Prifti, Philippe Froguel, The MetaCardis Consortium, Jean-Daniel Zucker, Fredrik Bäckhed, Henrik Vestergaard, Torben Hansen, Jean-Michel Oppert, Matthias Blüher, Jens Nielsen, Jeroen Raes, Peer Bork, Muhammad M. Yaqoob, Michael Stumvoll, Oluf Pedersen, S. Dusko Ehrlich, Karine Clément, and Marc-Emmanuel Dumas

Subjects
Science
Abstract

Abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Published
2023
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2. Comparison of bioresorbable vs durable polymer drug-eluting stents in unprotected left main (from the RAIN-CARDIOGROUP VII Study)

Author

Mario Iannaccone, Umberto Barbero, Michele De Benedictis, Yoichi Imori, Giorgio Quadri, Daniela Trabattoni, Nicola Ryan, Giuseppe Venuti, Andrea Montabone, Wojciech Wojakowski, Andrea Rognoni, Gerard Helft, Radoslaw Parma, Leonardo De Luca, Michele Autelli, Giacomo Boccuzzi, Alessio Mattesini, Christian Templin, Enrico Cerrato, Wojciech Wańha, Grzegorz Smolka, Zenon Huczek, Francesco Tomassini, Bernardo Cortese, Davide Capodanno, Alaide Chieffo, Ivan Nuñez-Gil, Sebastiano Gili, Antonia Bassignana, Carlo di Mario, Baldassarre Doronzo, Pierluigi Omedè, Maurizio D’Amico, Delio Tedeschi, Ferdinando Varbella, Thomas Luscher, Imad Sheiban, Javier Escaned, Mauro Rinaldi, and Fabrizio D’Ascenzo

Subjects
Percutaneous coronary intervention, Drug eluting stents, Struts thickness, Left main, Coronary bifurcation, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 μm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. Results From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12–22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. Conclusion In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. Trial registration ClinicalTrials.gov Identifier: NCT03544294 . Retrospectively registered June 1, 2018.

Published
2020
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3. Impact of Left Ventricular Ejection Fraction on Procedural and Long-Term Outcomes of Bifurcation Percutaneous Coronary Intervention

Author

Guglielmo Gallone, Jeehoon Kang, Francesco Bruno, Jung-Kyu Han, Ovidio De Filippo, Han-Mo Yang, Mattia Doronzo, Kyung-Woo Park, Gianluca Mittone, Hyun-Jae Kang, Radoslaw Parma, Hyeon-Cheol Gwon, Enrico Cerrato, Woo Jung Chun, Grzegorz Smolka, Seung-Ho Hur, Gerard Helft, Seung Hwan Han, Saverio Muscoli, Young Bin Song, Filippo Figini, Ki Hong Choi, Giacomo Boccuzzi, Soon-Jun Hong, Daniela Trabattoni, Chang-Wook Nam, Massimo Giammaria, Hyo-Soo Kim, Federico Conrotto, Javier Escaned, Carlo Di Mario, Fabrizio D'Ascenzo, Bon-Kwon Koo, Gaetano Maria de Ferrari, Università degli studi di Torino = University of Turin (UNITO), Seoul National University Hospital, Medical University of Silesia (SUM), Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Ospedale di Rivoli [Rivoli, Italy] (OR), Keimyung University, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gachon University Gil Medical Center [Incheon, Republic of Korea], University of Rome 'Tor Vergeta', Università degli Studi di Roma Tor Vergata [Roma], Clinica Pederzoli [Peschiera del Garda, Italy] (CP), Ospedale S.Giovanni Bosco, Korea University [Seoul], Monzino Cardiology Center [Milan, Italy] (M2C), Maria Vittoria Hospital [Turin], Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Careggi University Hospital [Florence, Italie], and Lesnik, Philippe

Subjects
[SDV] Life Sciences [q-bio], Ventricular Dysfunction, Left, Percutaneous Coronary Intervention, Treatment Outcome, [SDV]Life Sciences [q-bio], Humans, Drug-Eluting Stents, Stroke Volume, Coronary Artery Disease, Registries, Cardiology and Cardiovascular Medicine, Ventricular Function, Left, Retrospective Studies
Abstract

International audience; The association of left ventricular ejection fraction (LVEF) with procedural and long-term outcomes after state-of-the-art percutaneous coronary intervention (PCI) of bifurcation lesions remains unsettled. A total of 5,333 patients who underwent contemporary coronary bifurcation PCI were included in the intercontinental retrospective combined insights from the unified RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) and COBIS (COronary BIfurcation Stenting) III bifurcation registries. Of 5,003 patients (93.8%) with known baseline LVEF, 244 (4.9%) had LVEF

Published
2022

4. Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

Author

Antonio Molinaro, Ina Nemet, Pierre Bel Lassen, Rima Chakaroun, Trine Nielsen, Judith Aron-Wisnewsky, Per-Olof Bergh, Lin Li, Marcus Henricsson, Lars Køber, Richard Isnard, Gerard Helft, Michael Stumvoll, Oluf Pedersen, J. Gustav Smith, W.H. Wilson Tang, Karine Clément, Stanley L. Hazen, and Fredrik Bäckhed

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

6. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author

Sebastien Fromentin, Sofia K. Forslund, Kanta Chechi, Judith Aron-Wisnewsky, Rima Chakaroun, Trine Nielsen, Valentina Tremaroli, Boyang Ji, Edi Prifti, Antonis Myridakis, Julien Chilloux, Petros Andrikopoulos, Yong Fan, Michael T. Olanipekun, Renato Alves, Solia Adiouch, Noam Bar, Yeela Talmor-Barkan, Eugeni Belda, Robert Caesar, Luis Pedro Coelho, Gwen Falony, Soraya Fellahi, Pilar Galan, Nathalie Galleron, Gerard Helft, Lesley Hoyles, Richard Isnard, Emmanuelle Le Chatelier, Hanna Julienne, Lisa Olsson, Helle Krogh Pedersen, Nicolas Pons, Benoit Quinquis, Christine Rouault, Hugo Roume, Joe-Elie Salem, Thomas S. B. Schmidt, Sara Vieira-Silva, Peishun Li, Maria Zimmermann-Kogadeeva, Christian Lewinter, Nadja B. Søndertoft, Tue H. Hansen, Dominique Gauguier, Jens Peter Gøtze, Lars Køber, Ran Kornowski, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Serge Hercberg, Ivica Letunic, Fredrik Bäckhed, Jean-Michel Oppert, Jens Nielsen, Jeroen Raes, Peer Bork, Michael Stumvoll, Eran Segal, Karine Clément, Marc-Emmanuel Dumas, S. Dusko Ehrlich, Oluf Pedersen, Commission of the European Communities, Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Molecular Biology Laboratory [Heidelberg] (EMBL), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitätsklinikum Leipzig, IT University of Copenhagen (ITU), University of Gothenburg (GU), Chalmers University of Technology [Göteborg], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Imperial College London, Guangzhou Medical University, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Our study, Metagenomics in Cardiometabolic Diseases, with the acronym METACARDIS, was sponsored by the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312. Assistance Publique-Hôpitaux de Paris is the promoter of the clinical investigation. Parts of the studies were also supported by Metagenopolis grant ANR-11-DPBS-0001, the Leducq Foundation, the Novo Nordisk Foundation and the NIHR Imperial Biomedical Research Centre and by grants from the French National Research Agency (ANR-10-LABX-46 (European Genomics Institute for Diabetes)), the National Center for Precision Diabetic Medicine, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001), the European Union (FEDER), the Hauts-de-France Regional Council (Agreement 20001891/NP0025517), the European Metropolis of Lille (agreement 2019_ESR_11) and site ULNE (R-002-20-TALENT-DUMAS), which is also jointly funded by ANR (ANR-16-IDEX-0004-ULNE), the Hauts-de-France Regional Council (20002845) and the European Metropolis of Lille. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research institution at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation. K. Chechi is supported by the Medical Research Council Skills Development Fellowship (grant no. MR/S020039/1) and the Wellcome Trust-funded Institutional Strategic Support Fellowship (grant no. 204834/Z/16/Z). L.H. was in receipt of a Medical Research Council Intermediate Research Fellowship in Data Science (grant no. MR/L01632X/1, UK Med-Bio). S.K.F. was supported by the German Centre for Cardiovascular Research, the German Research Council (projects SFB1365, SFB1470 and KFO339) and the German Ministry of Education and Research., We are indebted to the MetaCardis study participants and patient associations (Alliance du Coeur and CNAO) for their input and interface. Similarly, we are indebted to the MetaCardis consortium (http://www.metacardis.net/) collaborators for contributions at multiple levels since the consortium start in 2012. A full list of collaborators is given in the Supplementary Information. We further thank D. Bonnefont-Rousselot (Department of Metabolic Biochemistry, Pitié-Salpêtrière Hospital) for the analysis of plasma lipid profiles. We greatly appreciate the assistance of nurses, dietitians, laboratory technicians, clinical research assistants and data managers at the Novo Nordisk Foundation Center for Basic Metabolic Research, the Clinical Research Unit at Fredriksberg and Bispebjerg Hospitals, Copenhagen, the Clinical Investigation Platform at the Institute of Cardiometabolism and Nutrition for Patient Investigations and the Clinical Investigation Center from Pitié-Salpêtrière Hospital, Paris, and the University of Leipzig Medical Center, Leipzig. Quanta Medical provided regulatory oversight of the clinical study and contributed to the processing and management of electronic data, ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), ANR-16-IDEX-0004,ULNE,ULNE(2016), European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
Biochemistry & Molecular Biology, IMPACT, [SDV]Life Sciences [q-bio], Immunology, Research & Experimental Medicine, General Biochemistry, Genetics and Molecular Biology, SERUM, Humans, Longitudinal Studies, cardiovascular diseases, SIGNATURES, 11 Medical and Health Sciences, P-CRESOL, RISK, Science & Technology, PLASMA, Microbiota, GUT MICROBIOTA, General Medicine, Cell Biology, Middle Aged, Medicine, Research & Experimental, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, Cardiovascular Diseases, Metabolome, CORONARY-ARTERY-DISEASE, HEART, HEALTH, Life Sciences & Biomedicine
Abstract

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features. ispartof: NATURE MEDICINE vol:28 issue:2 pages:303-+ ispartof: location:United States status: published

Published
2022

7. Effects of Aggressive Versus Conventional Lipid-Lowering Therapy by Simvastatin on Human Atherosclerotic Lesions

Author

Roberto Corti, Stephen G. Worthley, Gerard Helft, Juan F. Viles-Gonzalez, Juan J. Badimon, Valentin Fuster, Zahi A. Fayad, William F. Chaplin, Donald A. Smith, Gabor Mizsei, Jesse Weinberger, and Jörg Muntwyler

Subjects
medicine.medical_specialty, Aorta, Statin, medicine.diagnostic_test, business.industry, Vascular disease, medicine.drug_class, Urology, Magnetic resonance imaging, medicine.disease, Asymptomatic, Surgery, Lesion, Simvastatin, medicine.artery, Medicine, lipids (amino acids, peptides, and proteins), medicine.symptom, business, Prospective cohort study, Cardiology and Cardiovascular Medicine, medicine.drug
Abstract

Objectives This study sought to compare the effects of aggressive and conventional lipid lowering by two different dosages of the same statin on early human atherosclerotic lesions using serial noninvasive magnetic resonance imaging (MRI). Background Regression of atherosclerotic lesions by lipid-lowering therapy has been reported. Methods Using a double-blind design, newly diagnosed hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n = 22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57 carotid plaques were detected and sequentially followed up by MRI every six months after lipid-lowering initiation. The primary MRI end point was change in vessel wall area (VWA) as a surrogate for atherosclerotic burden. Results Both statin doses reduced significantly total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) versus baseline (p Conclusions Effective and protracted lipid-lowering therapy with simvastatin is associated with a significant regression of atherosclerotic lesions. No difference in vessel wall changes was seen between high and conventional doses of simvastatin. Changes in vessel wall parameters are more related to LDL-C reduction rather than to the dose of statin.

Published
2005
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8. Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging

Author

Roberto, Corti, Valentin, Fuster, Zahi A, Fayad, Stephen G, Worthley, Gerard, Helft, William F, Chaplin, Jörg, Muntwyler, Juan F, Viles-Gonzalez, Jesse, Weinberger, Donald A, Smith, Gabor, Mizsei, and Juan J, Badimon

Subjects
Adult, Aged, 80 and over, Male, Simvastatin, Time Factors, Dose-Response Relationship, Drug, Arteriosclerosis, Hypercholesterolemia, Aorta, Thoracic, Middle Aged, Magnetic Resonance Imaging, Carotid Arteries, Double-Blind Method, Humans, Female, Prospective Studies, Aged, Follow-Up Studies, Hypolipidemic Agents
Abstract

This study sought to compare the effects of aggressive and conventional lipid lowering by two different dosages of the same statin on early human atherosclerotic lesions using serial noninvasive magnetic resonance imaging (MRI).Regression of atherosclerotic lesions by lipid-lowering therapy has been reported.Using a double-blind design, newly diagnosed hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n = 22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57 carotid plaques were detected and sequentially followed up by MRI every six months after lipid-lowering initiation. The primary MRI end point was change in vessel wall area (VWA) as a surrogate for atherosclerotic burden.Both statin doses reduced significantly total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) versus baseline (p0.001). Total cholesterol decreased by 26% versus 33% and LDL-C by 36% versus 46% in the conventional (20 mg) versus aggressive (80 mg) simvastatin groups, respectively. Although the simvastatin 80-mg group had significantly higher baseline TC and LDL-C levels, both groups reached similar absolute values after treatment. A significant reduction in VWA was already observed by 12 months. No difference on vascular effects was detected between the randomized doses. Post-hoc analysis showed that patients reaching mean on-treatment LDL-Cor = 100 mg/dl had larger decreases in plaque size.Effective and protracted lipid-lowering therapy with simvastatin is associated with a significant regression of atherosclerotic lesions. No difference in vessel wall changes was seen between high and conventional doses of simvastatin. Changes in vessel wall parameters are more related to LDL-C reduction rather than to the dose of statin.

Published
2004

9. Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation.

Author

Zhuangyu Zhang, Josef Machac, Gerard Helft, Stephen G. Worthley, Cheuk Tang, Azfar G. Zaman, Oswaldo J. Rodriguez, Monte S. Buchsbaum, Valentin Fuster, and Juan J.Badimon

Subjects
ATHEROSCLEROSIS, MYOCARDIAL infarction, CORONARY disease, ATHEROSCLEROTIC plaque, MAGNETIC resonance imaging, RADIOACTIVITY, NUCLEAR medicine
Abstract

Background: Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model. Methods: Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta. Results: Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity. Conclusion: PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion. [ABSTRACT FROM AUTHOR]

Published
2006
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10. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Ivica Letunic, Pilar Galan, Karen E. Assmann, Gwen Falony, Nicolas Pons, Fredrik Bäckhed, Trine Nielsen, Per-Olof Bergh, Lars Køber, Jens Nielsen, S. Dusko Ehrlich, Eugeni Belda, Henrik Vestergaard, Edi Prifti, Florian Marquet, Marc-Emmanuel Dumas, Jean-Michel Oppert, Michael Stumvoll, Sara Vieira-Silva, Pierre Bel Lassen, Jeroen Raes, Helle Krogh Pedersen, Judith Aron-Wisnewsky, Torben Hansen, Antonio Molinaro, Peer Bork, Oluf Pedersen, Christine Rouault, Benoit Quinquis, Christian Lewinter, Joe-Elie Salem, Rima Chakaroun, Tue H. Hansen, Fabrizio Andreelli, Hao Wu, Nadja B Sønderskov, Solia Adriouch, Sébastien André, Karine Clément, Jean-Daniel Zucker, Marcus Henricsson, Hugo Roume, Sofia K. Forslund, Jean-Philippe Bastard, University of Gothenburg (GU), Sahlgrenska University Hospital [Gothenburg], Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Universität Leipzig, University of Copenhagen = Københavns Universitet (UCPH), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), VIB-KU Leuven Center for Microbiology [Leuven, Belgium], Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Imperial College London, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Biobyte Solutions GMBH, Chalmers University of Technology [Gothenburg, Sweden], European Molecular Biology Laboratory [Heidelberg] (EMBL), Universität Heidelberg [Heidelberg] = Heidelberg University, MetaCardis Consortium: Renato Alves, Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Olivier Barthelemy, Jean-Paul Batisse, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Julien Chilloux, Cecile Ciangura, Luis Pedro Coelho, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Leopold Fezeu, Sebastien Fromentin, Philippe Giral, Jens Peter Gøtze, Agnes Hartemann, Jens Juul Holst, Serge Hercberg, Gerard Helft, Malene Hornbak, Jean-Sebastien Hulot, Richard Isnard, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Nadja Buus Kristensen, Michael Kuhn, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moutel, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Sebastien Schmidt, Lucas Moitinho-Silva, Johanne Silvain, Nataliya Sokolovska, Sothea Touch, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., Lesnik, Philippe, Universität Leipzig [Leipzig], Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Universität Heidelberg [Heidelberg]

Subjects
Multidisciplinary, Imidazole propionate, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, Pharmacology, Biology, medicine.disease, General Biochemistry, Genetics and Molecular Biology, [SDV] Life Sciences [q-bio], Microbial ecology, Diabetes mellitus, medicine
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20412-9.

Published
2020

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