Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications
Introduction: The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not w...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Molecular and Cellular Cardiology Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772976124000023 |
| _version_ | 1797258665701408768 |
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| author | B. Srinivas K. Alluri H. Peng P.A. Ortiz J. Xu H.N. Sabbah N.E. Rhaleb K. Matrougui |
| author_facet | B. Srinivas K. Alluri H. Peng P.A. Ortiz J. Xu H.N. Sabbah N.E. Rhaleb K. Matrougui |
| author_sort | B. Srinivas |
| collection | DOAJ |
| description | Introduction: The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction. Methods: Eight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N[w]-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function. Results: Female mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction. Conclusions: We found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present. |
| first_indexed | 2024-03-08T14:20:14Z |
| format | Article |
| id | doaj.art-7d073575785d4baabda9c14e41ba9a31 |
| institution | Directory Open Access Journal |
| issn | 2772-9761 |
| language | English |
| last_indexed | 2024-04-24T22:57:09Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Molecular and Cellular Cardiology Plus |
| spelling | doaj.art-7d073575785d4baabda9c14e41ba9a312024-03-18T04:34:56ZengElsevierJournal of Molecular and Cellular Cardiology Plus2772-97612024-03-017100062Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complicationsB. Srinivas0K. Alluri1H. Peng2P.A. Ortiz3J. Xu4H.N. Sabbah5N.E. Rhaleb6K. Matrougui7Department of Physiological Sciences, EVMS, Norfolk, VA 23501, USADepartment of Physiological Sciences, EVMS, Norfolk, VA 23501, USADepartment of Physiology, Wayne State University, Detroit, MI 48202, USA; Internal Medicine Department, Hypertension and Vascular Research, Detroit, MI 48202, USADepartment of Physiology, Wayne State University, Detroit, MI 48202, USA; Internal Medicine Department, Hypertension and Vascular Research, Detroit, MI 48202, USAInternal Medicine Department, Cardiovascular Medicine, Detroit, MI 48202, USAInternal Medicine Department, Cardiovascular Medicine, Detroit, MI 48202, USADepartment of Physiology, Wayne State University, Detroit, MI 48202, USA; Internal Medicine Department, Cardiovascular Medicine, Detroit, MI 48202, USADepartment of Physiological Sciences, EVMS, Norfolk, VA 23501, USA; Corresponding author.Introduction: The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction. Methods: Eight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N[w]-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function. Results: Female mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction. Conclusions: We found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present.http://www.sciencedirect.com/science/article/pii/S2772976124000023HFpEFFemale miceVascular endothelia dysfunctionKidney failureInflammationER stress |
| spellingShingle | B. Srinivas K. Alluri H. Peng P.A. Ortiz J. Xu H.N. Sabbah N.E. Rhaleb K. Matrougui Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications Journal of Molecular and Cellular Cardiology Plus HFpEF Female mice Vascular endothelia dysfunction Kidney failure Inflammation ER stress |
| title | Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications |
| title_full | Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications |
| title_fullStr | Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications |
| title_full_unstemmed | Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications |
| title_short | Unveiling the vulnerability of C57BL/6J female mice to HFpEF and its related complications |
| title_sort | unveiling the vulnerability of c57bl 6j female mice to hfpef and its related complications |
| topic | HFpEF Female mice Vascular endothelia dysfunction Kidney failure Inflammation ER stress |
| url | http://www.sciencedirect.com/science/article/pii/S2772976124000023 |
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