Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats
Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting with an ejection fraction (EF) of greater than 50% along with different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understandin...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1157398/full |
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| author | Saltanat Zhazykbayeva Saltanat Zhazykbayeva Saltanat Zhazykbayeva Roua Hassoun Roua Hassoun Roua Hassoun Melissa Herwig Melissa Herwig Melissa Herwig Heidi Budde Heidi Budde Heidi Budde Árpád Kovács Árpád Kovács Árpád Kovács Hans Georg Mannherz Hans Georg Mannherz Hans Georg Mannherz Ibrahim El-Battrawy Ibrahim El-Battrawy Ibrahim El-Battrawy Attila Tóth Attila Tóth Wolfgang E. Schmidt Andreas Mügge Andreas Mügge Andreas Mügge Nazha Hamdani Nazha Hamdani Nazha Hamdani |
| author_facet | Saltanat Zhazykbayeva Saltanat Zhazykbayeva Saltanat Zhazykbayeva Roua Hassoun Roua Hassoun Roua Hassoun Melissa Herwig Melissa Herwig Melissa Herwig Heidi Budde Heidi Budde Heidi Budde Árpád Kovács Árpád Kovács Árpád Kovács Hans Georg Mannherz Hans Georg Mannherz Hans Georg Mannherz Ibrahim El-Battrawy Ibrahim El-Battrawy Ibrahim El-Battrawy Attila Tóth Attila Tóth Wolfgang E. Schmidt Andreas Mügge Andreas Mügge Andreas Mügge Nazha Hamdani Nazha Hamdani Nazha Hamdani |
| author_sort | Saltanat Zhazykbayeva |
| collection | DOAJ |
| description | Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting with an ejection fraction (EF) of greater than 50% along with different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understanding of HFpEF, effective treatments are still limited. In the current study we attempted to unravel the molecular basis of sex-dependent differences in HFpEF pathology. We analyzed left ventricular samples from 1-year-old female and male transgenic (TG) rats homozygous for the rat Ren-2 renin gene (mRen2) characterized with hypertension and diastolic dysfunction and compared it to age-matched female and male wild type rats (WT) served as control. Cardiomyocytes from female and male TG rats exhibited an elevated titin-based stiffness (Fpassive), which was corrected to control level upon treatment with reduced glutathione indicating titin oxidation. This was accompanied with high levels of oxidative stress in TG rats with more prominent effects in female group. In vitro supplementation with heat shock proteins (HSPs) reversed the elevated Fpassive indicating restoration of their cytoprotective function. Furthermore, the TG group exhibited high levels of proinflammatory cytokines with significant alterations in apoptotic and autophagy pathways in both sexes. Distinct alterations in the expression of several proteins between both sexes suggest their differential impact on disease development and necessitate distinct treatment options. Hence, our data suggested that oxidative stress and inflammation distinctly drive diastolic dysfunction and remodeling in female and male rats with HFpEF and that the sex-dependent mechanisms contribute to HF pathology. |
| first_indexed | 2024-03-13T06:45:47Z |
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| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-13T06:45:47Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-7ec97b2fac2b4eff83a689c7e3e654072023-06-08T06:16:00ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-06-011010.3389/fcvm.2023.11573981157398Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction ratsSaltanat Zhazykbayeva0Saltanat Zhazykbayeva1Saltanat Zhazykbayeva2Roua Hassoun3Roua Hassoun4Roua Hassoun5Melissa Herwig6Melissa Herwig7Melissa Herwig8Heidi Budde9Heidi Budde10Heidi Budde11Árpád Kovács12Árpád Kovács13Árpád Kovács14Hans Georg Mannherz15Hans Georg Mannherz16Hans Georg Mannherz17Ibrahim El-Battrawy18Ibrahim El-Battrawy19Ibrahim El-Battrawy20Attila Tóth21Attila Tóth22Wolfgang E. Schmidt23Andreas Mügge24Andreas Mügge25Andreas Mügge26Nazha Hamdani27Nazha Hamdani28Nazha Hamdani29Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Anatomy and Molecular Embryology, Ruhr University Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology and Angiology, Bergmannsheil University Hospitals, UK RUB, Ruhr University of Bochum, Bochum, GermanyDivision of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, HungaryResearch Centre for Molecular Medicine, University of Debrecen, Debrecen, HungaryDepartment of Medicine I, St. Josef Hospital, UK RUB, Ruhr-University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology and Angiology, Bergmannsheil University Hospitals, UK RUB, Ruhr University of Bochum, Bochum, GermanyDepartment of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, GermanyInstitut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, GermanyDepartment of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, GermanyHeart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting with an ejection fraction (EF) of greater than 50% along with different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understanding of HFpEF, effective treatments are still limited. In the current study we attempted to unravel the molecular basis of sex-dependent differences in HFpEF pathology. We analyzed left ventricular samples from 1-year-old female and male transgenic (TG) rats homozygous for the rat Ren-2 renin gene (mRen2) characterized with hypertension and diastolic dysfunction and compared it to age-matched female and male wild type rats (WT) served as control. Cardiomyocytes from female and male TG rats exhibited an elevated titin-based stiffness (Fpassive), which was corrected to control level upon treatment with reduced glutathione indicating titin oxidation. This was accompanied with high levels of oxidative stress in TG rats with more prominent effects in female group. In vitro supplementation with heat shock proteins (HSPs) reversed the elevated Fpassive indicating restoration of their cytoprotective function. Furthermore, the TG group exhibited high levels of proinflammatory cytokines with significant alterations in apoptotic and autophagy pathways in both sexes. Distinct alterations in the expression of several proteins between both sexes suggest their differential impact on disease development and necessitate distinct treatment options. Hence, our data suggested that oxidative stress and inflammation distinctly drive diastolic dysfunction and remodeling in female and male rats with HFpEF and that the sex-dependent mechanisms contribute to HF pathology.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1157398/fulldiastolic dysfunctionsex differencesmechanismsoxidative stressinflammation |
| spellingShingle | Saltanat Zhazykbayeva Saltanat Zhazykbayeva Saltanat Zhazykbayeva Roua Hassoun Roua Hassoun Roua Hassoun Melissa Herwig Melissa Herwig Melissa Herwig Heidi Budde Heidi Budde Heidi Budde Árpád Kovács Árpád Kovács Árpád Kovács Hans Georg Mannherz Hans Georg Mannherz Hans Georg Mannherz Ibrahim El-Battrawy Ibrahim El-Battrawy Ibrahim El-Battrawy Attila Tóth Attila Tóth Wolfgang E. Schmidt Andreas Mügge Andreas Mügge Andreas Mügge Nazha Hamdani Nazha Hamdani Nazha Hamdani Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats Frontiers in Cardiovascular Medicine diastolic dysfunction sex differences mechanisms oxidative stress inflammation |
| title | Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats |
| title_full | Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats |
| title_fullStr | Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats |
| title_full_unstemmed | Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats |
| title_short | Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats |
| title_sort | oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats |
| topic | diastolic dysfunction sex differences mechanisms oxidative stress inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1157398/full |
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