المؤلفون: Ferreira, João Pedro, Packer, Milton, Butler, Javed, Filippatos, Gerasimos, Pocock, Stuart, J., Januzzi, James, L., Sattar, Naveed, Maldonado, Sandra González, Panova-Noeva, Marina, Sumin, Mikhail, Masson, Serge, Anker, Stefan, D., Zannad, Faiez

المساهمون: Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin Nancy (CIC-P), Centre d'investigation clinique Nancy (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists Vandoeuvre-les-Nancy (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu Nancy, French-Clinical Research Infrastructure Network - F-CRIN Paris (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular R&D Centre-UnIC@RISE, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Internal Medicine Department, Heart Failure Clinic, Centro Hospitalar de Vila Nova de Gaia/Espinho, Baylor University Medical Center, Baylor College of Medecine, Imperial College London, Baylor Scott & White Research Institute (BSWRI), University of Mississippi Medical Center (UMMC), “Attikon” University Hospital, National and Kapodistrian University of Athens (NKUA), London School of Hygiene and Tropical Medicine (LSHTM), Massachusetts General Hospital Boston, Baim Institute for Clinical Research Boston MA, University of Glasgow, Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim International GmbH, Roche Diagnostics International Ltd, Berlin-Brandenburg Center for Regenerative Medicine Berlin, Germany (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital Berlin, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), The EMPEROR-Reduced and Preserved trials were funded by Boehringer Ingelheim and Eli Lilly (EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977 and EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951)

المصدر: ISSN: 1388-9842 ; European Journal of Heart Failure ; https://hal.univ-lorraine.fr/hal-04317427Test ; European Journal of Heart Failure, 2023, ⟨10.1002/ejhf.3078⟩.

مصطلحات موضوعية: Growth differentiation factor-15 Heart failure Empagliflozin Metformin, Growth differentiation factor-15, Heart failure, Empagliflozin, Metformin, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Aims Growth differentiation factor‐15 (GDF‐15) is upregulated in part in response to cardiomyocyte stretch and stress, and it exerts a protective role that is mediated by its action to suppress signalling through insulin‐like growth factor (IGF) and enhance signalling through adenosine monophosphate‐activated protein kinase (AMPK). Sodium–glucose cotransporter 2 (SGLT2) inhibitors improve outcomes in heart failure, which has been experimentally linked to AMPK. This study aimed at evaluating the associations of GDF‐15 with baseline characteristics, the prognostic significance of GDF‐15, and the effect of empagliflozin on GDF‐15 in patients with heart failure with a reduced and preserved ejection fraction. Methods and results Growth differentiation factor‐15 was determined in serum samples from the EMPEROR‐Reduced and EMPEROR‐Preserved trials. Cox regression and mixed models for repeated measures were used to study the association with outcomes and the effect of empagliflozin on GDF‐15, respectively. We studied 1124 patients (560 placebo and 564 empagliflozin) with median GDF‐15 levels at baseline of 2442 (interquartile range 1603–3780) pg/ml. Patients with higher GDF‐15 levels were typically older men with more severe symptoms, higher N‐terminal pro‐B‐type natriuretic peptide levels, worse kidney function and who were prescribed metformin. Baseline levels of GDF‐15 were well correlated with levels of IGF‐binding protein 7 (rho = 0.64). Higher levels of GDF‐15 were independently associated with an increased risk of cardiovascular death, heart failure hospitalizations, and worse kidney outcomes. When considered as a continuous variable, for each doubling in GDF‐15, the adjusted hazard ratio for cardiovascular death or heart failure hospitalization was 1.40 (95% confidence interval 1.15–1.71; p < 0.001). The relative effect of empagliflozin on cardiovascular death and hospitalization for heart failure was most pronounced in patients with higher baseline levels of GDF‐15 (interaction p ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37964408; hal-04317427; https://hal.univ-lorraine.fr/hal-04317427Test; https://hal.univ-lorraine.fr/hal-04317427/documentTest; https://hal.univ-lorraine.fr/hal-04317427/file/European%20J%20of%20Heart%20Fail%20-%202023%20-%20Ferreira%20-%20Growth%20differentiation%20factor%E2%80%9015%20and%20the%20effect%20of%20empagliflozin%20in%20heart.pdfTest; PUBMED: 37964408

الإتاحة: https://doi.org/10.1002/ejhf.3078Test
https://hal.univ-lorraine.fr/hal-04317427Test
https://hal.univ-lorraine.fr/hal-04317427/documentTest
https://hal.univ-lorraine.fr/hal-04317427/file/European%20J%20of%20Heart%20Fail%20-%202023%20-%20Ferreira%20-%20Growth%20differentiation%20factor%E2%80%9015%20and%20the%20effect%20of%20empagliflozin%20in%20heart.pdfTest

المؤلفون: Wischhusen, Jörg, Melero, Ignacio, Fridman, Wolf, Herman

المساهمون: University Hospital of Würzburg, Center for Applied Medical Research Plamplona (CIMA), Universidad de Navarra Pamplona (UNAV), Clínica Universidad de Navarra Pamplona, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)

المصدر: ISSN: 1664-3224.

مصطلحات موضوعية: anorexia, autoimmunity, cancer, growth/differentiation factor-15 (GDF-15), immune exclusion, immunotherapy, macrophage inhibitory cytokine-1 (MIC-1), pregnancy, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity

الوصف: International audience ; Growth/differentiation factor-15 (GDF-15), also named macrophage inhibitory cytokine-1, is a divergent member of the transforming growth factor β superfamily. While physiological expression is barely detectable in most somatic tissues in humans, GDF-15 is abundant in placenta. Elsewhere, GDF-15 is often induced under stress conditions, seemingly to maintain cell and tissue homeostasis; however, a moderate increase in GDF-15 blood levels is observed with age. Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer. GDF-15 has thus been widely explored as a biomarker for disease prognosis. Mechanistically, induction of anorexia via the brainstem-restricted GDF-15 receptor GFRAL (glial cell-derived neurotrophic factor [GDNF] family receptor α-like) is well-documented. GDF-15 and GFRAL have thus become attractive targets for metabolic intervention. Still, several GDF-15 mediated effects (including its physiological role in pregnancy) are difficult to explain via the described pathway. Hence, there is a clear need to better understand non-metabolic effects of GDF-15. With particular emphasis on its immunomodulatory potential this review discusses the roles of GDF-15 in pregnancy and in pathological conditions including myocardial infarction, autoimmune disease, and specifically cancer. Importantly, the strong predictive value of GDF-15 as biomarker may plausibly be linked to its immune-regulatory function. The described associations and mechanistic data support the hypothesis that GDF-15 acts as immune checkpoint and is thus an emerging target for cancer immunotherapy.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32508832; hal-02878344; https://hal.sorbonne-universite.fr/hal-02878344Test; https://hal.sorbonne-universite.fr/hal-02878344/documentTest; https://hal.sorbonne-universite.fr/hal-02878344/file/fimmu-11-00951.pdfTest; PUBMED: 32508832; PUBMEDCENTRAL: PMC7248355

الإتاحة: https://doi.org/10.3389/fimmu.2020.00951Test
https://hal.sorbonne-universite.fr/hal-02878344Test
https://hal.sorbonne-universite.fr/hal-02878344/documentTest
https://hal.sorbonne-universite.fr/hal-02878344/file/fimmu-11-00951.pdfTest

المؤلفون: Verdonschot, Job A. J., Ferreira, João Pedro, Pellicori, Pierpaolo, Brunner-La Rocca, Hans-Peter, Clark, Andrew L., Cosmi, Franco, Cuthbert, Joe, Girerd, Nicolas, Mariottoni, Beatrice, Petutschnigg, Johannes, Rossignol, Patrick, Cleland, John G. F., Zannad, Faiez, Heymans, Stephane R. B., HOMAGE \\'Heart Omics in AGEing\\' consortium

المساهمون: Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Glasgow, Institute of Health and Wellbeing, University of Glasgow-Gartnavel General Hospital, Glasgow, Robertson Centre for Biostatistics & Clinical Trials Unit, University of Hull [United Kingdom], Castle Hill Hospital, Cortona Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Charité Campus Virchow-Klinikum (CVK), Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), The research leading to these results has received funding from the EuropeanUnion Commission’s Seventh Framework programme under Grant AgreementNo. 305507 (HOMAGE). S.H: This manuscript has been possible thanks to thesupport of the Netherlands Cardiovascular Research Initiative, an initiativewith support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10,CVON She-PREDICTS, Grant 2017-21., European Project: 305507, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9)

المصدر: Cardiovascular Diabetology
Cardiovascular Diabetology, BioMed Central, 2021, 20 (1), pp.163. ⟨10.1186/s12933-021-01357-9⟩
Cardiovascular Diabetology, Vol 20, Iss 1, Pp 1-10 (2021)
Cardiovascular Diabetology, 20(1):163. BioMed Central Ltd

مصطلحات موضوعية: Male, Proteomics, Cardiac & Cardiovascular Systems, Time Factors, Proteome, Diabetic Cardiomyopathies, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Spironolactone, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Natriuretic peptide, Prospective Studies, Original Investigation, Mineralocorticoid Receptor Antagonists, 0303 health sciences, Diabetes, Blood Proteins, GROWTH-DIFFERENTIATION FACTOR-15, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, Biomarker (medicine), Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, medicine.drug_class, Heart failure, Risk Assessment, 03 medical and health sciences, Endocrinology & Metabolism, INFLAMMATION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Diseases of the circulatory (Cardiovascular) system, Humans, 030304 developmental biology, Aged, Proteomic Profile, Science & Technology, business.industry, Biomarker, medicine.disease, Omics, Fibrosis, Blood pressure, chemistry, RC666-701, Cardiovascular System & Cardiology, business, Biomarkers

الوصف: Background Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The “Heart OMics in AGEing” (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial. Methods Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes. Results Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05). Conclusions Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.

وصف الملف: Electronic; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df652958d7e94ce09add8331ace3234fTest
https://hal.univ-lorraine.fr/hal-03320862/documentTest