Sex differences in circulating proteins in heart failure with preserved ejection fraction
Abstract Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients ar...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-08-01
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| Series: | Biology of Sex Differences |
| Online Access: | http://link.springer.com/article/10.1186/s13293-020-00322-7 |
| _version_ | 1819195159549575168 |
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| author | Susan Stienen João Pedro Ferreira Masatake Kobayashi Gregoire Preud’homme Daniela Dobre Jean-Loup Machu Kevin Duarte Emmanuel Bresso Marie-Dominique Devignes Natalia López Andrés Nicolas Girerd Svend Aakhus Giuseppe Ambrosio Hans-Peter Brunner-La Rocca Ricardo Fontes-Carvalho Alan G. Fraser Loek van Heerebeek Gilles de Keulenaer Paolo Marino Kenneth McDonald Alexandre Mebazaa Zoltàn Papp Riccardo Raddino Carsten Tschöpe Walter J. Paulus Faiez Zannad Patrick Rossignol |
| author_facet | Susan Stienen João Pedro Ferreira Masatake Kobayashi Gregoire Preud’homme Daniela Dobre Jean-Loup Machu Kevin Duarte Emmanuel Bresso Marie-Dominique Devignes Natalia López Andrés Nicolas Girerd Svend Aakhus Giuseppe Ambrosio Hans-Peter Brunner-La Rocca Ricardo Fontes-Carvalho Alan G. Fraser Loek van Heerebeek Gilles de Keulenaer Paolo Marino Kenneth McDonald Alexandre Mebazaa Zoltàn Papp Riccardo Raddino Carsten Tschöpe Walter J. Paulus Faiez Zannad Patrick Rossignol |
| author_sort | Susan Stienen |
| collection | DOAJ |
| description | Abstract Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83–2.63), p = 0.18. Conclusion In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF. |
| first_indexed | 2024-12-23T02:08:20Z |
| format | Article |
| id | doaj.art-f703a16e1f8a42f888984342fa27bfff |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-12-23T02:08:20Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-f703a16e1f8a42f888984342fa27bfff2022-12-21T18:03:51ZengBMCBiology of Sex Differences2042-64102020-08-0111111410.1186/s13293-020-00322-7Sex differences in circulating proteins in heart failure with preserved ejection fractionSusan Stienen0João Pedro Ferreira1Masatake Kobayashi2Gregoire Preud’homme3Daniela Dobre4Jean-Loup Machu5Kevin Duarte6Emmanuel Bresso7Marie-Dominique Devignes8Natalia López Andrés9Nicolas Girerd10Svend Aakhus11Giuseppe Ambrosio12Hans-Peter Brunner-La Rocca13Ricardo Fontes-Carvalho14Alan G. Fraser15Loek van Heerebeek16Gilles de Keulenaer17Paolo Marino18Kenneth McDonald19Alexandre Mebazaa20Zoltàn Papp21Riccardo Raddino22Carsten Tschöpe23Walter J. Paulus24Faiez Zannad25Patrick Rossignol26Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)LORIA (CNRS, Inria NGE, Université de Lorraine), Campus ScientifiqueLORIA (CNRS, Inria NGE, Université de Lorraine), Campus ScientifiqueNavarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNAUniversité de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Oslo University HospitalDivision of Cardiology, University of Perugia School of MedicineDepartment of Cardiology, Maastricht University Medical CenterDepartment of Surgery and Physiology, Cardiovascular Research Unit (UnIC), Faculty of Medicine, University of PortoWales Heart Research Institute, Cardiff UniversityDepartment of Cardiology, Onze Lieve Vrouwe GasthuisLaboratory of Physiopharmacology, Antwerp University and ZNA HartcentrumClinical Cardiology, Università del Piemonte Orientale, Department of Translational Medicine, Azienda Ospedaliero Universitaria “Maggiore della Carità”St Michael’s Hospital Dun Laoghaire Co. DublinDepartment of Anaesthesiology and Critical Care Medicine, Saint Louis and Lariboisière University Hospitals and INSERM UMR-S 942Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of DebrecenDepartment of Cardiology, Spedali Civili di BresciaDepartment of Cardiology, Campus Virchow-Klinikum, Charite Universitaetsmedizin Berlin, Berlin Institute of Health – Center for Regenerative Therapies (BIH-BCRT), and the German Center for Cardiovascular Research (DZHK ; Berlin partner site)Amsterdam Cardiovascular Sciences, Amsterdam University Medical CentersUniversité de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)Abstract Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83–2.63), p = 0.18. Conclusion In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.http://link.springer.com/article/10.1186/s13293-020-00322-7 |
| spellingShingle | Susan Stienen João Pedro Ferreira Masatake Kobayashi Gregoire Preud’homme Daniela Dobre Jean-Loup Machu Kevin Duarte Emmanuel Bresso Marie-Dominique Devignes Natalia López Andrés Nicolas Girerd Svend Aakhus Giuseppe Ambrosio Hans-Peter Brunner-La Rocca Ricardo Fontes-Carvalho Alan G. Fraser Loek van Heerebeek Gilles de Keulenaer Paolo Marino Kenneth McDonald Alexandre Mebazaa Zoltàn Papp Riccardo Raddino Carsten Tschöpe Walter J. Paulus Faiez Zannad Patrick Rossignol Sex differences in circulating proteins in heart failure with preserved ejection fraction Biology of Sex Differences |
| title | Sex differences in circulating proteins in heart failure with preserved ejection fraction |
| title_full | Sex differences in circulating proteins in heart failure with preserved ejection fraction |
| title_fullStr | Sex differences in circulating proteins in heart failure with preserved ejection fraction |
| title_full_unstemmed | Sex differences in circulating proteins in heart failure with preserved ejection fraction |
| title_short | Sex differences in circulating proteins in heart failure with preserved ejection fraction |
| title_sort | sex differences in circulating proteins in heart failure with preserved ejection fraction |
| url | http://link.springer.com/article/10.1186/s13293-020-00322-7 |
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