Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury
Abstract Background Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI i...
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BMC
2025-01-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-024-00673-5 |
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| author | Achi Haider Susan Bengs Angela Portmann Sandro Fröhlich Dominik Etter Monika Maredziak Geoffrey I. Warnock Alexander Akhmedov Sebastian Kozerke Claudia Keller Fabrizio Montecucco Bruno Weber Linjing Mu Ronny R. Buechel Vera Regitz-Zagrosek Philipp A. Kaufmann Giovanni G. Camici Simon M. Ametamey Catherine Gebhard |
| author_facet | Achi Haider Susan Bengs Angela Portmann Sandro Fröhlich Dominik Etter Monika Maredziak Geoffrey I. Warnock Alexander Akhmedov Sebastian Kozerke Claudia Keller Fabrizio Montecucco Bruno Weber Linjing Mu Ronny R. Buechel Vera Regitz-Zagrosek Philipp A. Kaufmann Giovanni G. Camici Simon M. Ametamey Catherine Gebhard |
| author_sort | Achi Haider |
| collection | DOAJ |
| description | Abstract Background Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI in younger women, however, the impact of sex hormones on these parameters remains unknown. Methods The effect of sex hormones and age on myocardial infarct size and myocardial sympathetic activity (MSA) was assessed in male and female, as well as young (4–6 months) and aged (20–22 months) FVB/N mice (n = 106, 60 gonadectomized and 46 sham-operated animals) who underwent in vivo [11C]meta-hydroxyephedrine ([11C]mHED) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging 24 h after a 30 min myocardial ischemic injury. Results MSA and catecholamine levels following myocardial injury were highest in young males (p = 0.008 and p = 0.043 vs. young females, respectively) and were reduced by orchiectomy. Accordingly, testosterone serum levels correlated positively with MSA (r = 0.66, p < 0.001). Males had a larger average infarct size and lower left ventricular contractility following myocardial injury than females (p < 0.05 vs. females). These sex differences were no longer evident in gonadectomized animals (p = NS vs. females). In female animals, estrogen depletion did not affect MSA (ovariectomy effect, p = 0.892). Female animals showed an age-dependent increase in MSA (p = 0.011), which was absent in males. Conclusion Testosterone associates with an increase in sympathetic tone, contributing to adverse cardiac remodeling following MI. Conversely, females maintain sympathetic integrity, independent of sex hormones. Our results suggest a biological advantage of female sex in post MI recovery. Further research is warranted to confirm these findings in humans. |
| format | Article |
| id | doaj-art-93b90ea521bf4fb8ba90a5f56d10be7e |
| institution | Kabale University |
| issn | 2042-6410 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Biology of Sex Differences |
| spelling | doaj-art-93b90ea521bf4fb8ba90a5f56d10be7e2025-01-19T12:05:12ZengBMCBiology of Sex Differences2042-64102025-01-0116111510.1186/s13293-024-00673-5Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injuryAchi Haider0Susan Bengs1Angela Portmann2Sandro Fröhlich3Dominik Etter4Monika Maredziak5Geoffrey I. Warnock6Alexander Akhmedov7Sebastian Kozerke8Claudia Keller9Fabrizio Montecucco10Bruno Weber11Linjing Mu12Ronny R. Buechel13Vera Regitz-Zagrosek14Philipp A. Kaufmann15Giovanni G. Camici16Simon M. Ametamey17Catherine Gebhard18Department of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichCenter for Molecular Cardiology, University of ZurichInstitute for Biomedical Engineering, University and ETH ZurichInstitute of Pharmaceutical Sciences, ETH ZurichFirst Clinic of Internal Medicine, Department of Internal Medicine, University of GenoaInstitute of Pharmacology and Toxicology, University of ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichInstitute for Gender in Medicine, Charité Universitaetsmedizin BerlinDepartment of Nuclear Medicine, University Hospital ZurichCenter for Molecular Cardiology, University of ZurichInstitute of Pharmaceutical Sciences, ETH ZurichDepartment of Nuclear Medicine, University Hospital ZurichAbstract Background Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI in younger women, however, the impact of sex hormones on these parameters remains unknown. Methods The effect of sex hormones and age on myocardial infarct size and myocardial sympathetic activity (MSA) was assessed in male and female, as well as young (4–6 months) and aged (20–22 months) FVB/N mice (n = 106, 60 gonadectomized and 46 sham-operated animals) who underwent in vivo [11C]meta-hydroxyephedrine ([11C]mHED) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging 24 h after a 30 min myocardial ischemic injury. Results MSA and catecholamine levels following myocardial injury were highest in young males (p = 0.008 and p = 0.043 vs. young females, respectively) and were reduced by orchiectomy. Accordingly, testosterone serum levels correlated positively with MSA (r = 0.66, p < 0.001). Males had a larger average infarct size and lower left ventricular contractility following myocardial injury than females (p < 0.05 vs. females). These sex differences were no longer evident in gonadectomized animals (p = NS vs. females). In female animals, estrogen depletion did not affect MSA (ovariectomy effect, p = 0.892). Female animals showed an age-dependent increase in MSA (p = 0.011), which was absent in males. Conclusion Testosterone associates with an increase in sympathetic tone, contributing to adverse cardiac remodeling following MI. Conversely, females maintain sympathetic integrity, independent of sex hormones. Our results suggest a biological advantage of female sex in post MI recovery. Further research is warranted to confirm these findings in humans.https://doi.org/10.1186/s13293-024-00673-5Myocardial infarctionSex hormonesSex[11C]meta-hydroxyephedrinePositron emission tomography (PET)Cardiac magnetic resonance (CMR) imaging |
| spellingShingle | Achi Haider Susan Bengs Angela Portmann Sandro Fröhlich Dominik Etter Monika Maredziak Geoffrey I. Warnock Alexander Akhmedov Sebastian Kozerke Claudia Keller Fabrizio Montecucco Bruno Weber Linjing Mu Ronny R. Buechel Vera Regitz-Zagrosek Philipp A. Kaufmann Giovanni G. Camici Simon M. Ametamey Catherine Gebhard Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury Biology of Sex Differences Myocardial infarction Sex hormones Sex [11C]meta-hydroxyephedrine Positron emission tomography (PET) Cardiac magnetic resonance (CMR) imaging |
| title | Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury |
| title_full | Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury |
| title_fullStr | Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury |
| title_full_unstemmed | Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury |
| title_short | Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury |
| title_sort | age and sex specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury |
| topic | Myocardial infarction Sex hormones Sex [11C]meta-hydroxyephedrine Positron emission tomography (PET) Cardiac magnetic resonance (CMR) imaging |
| url | https://doi.org/10.1186/s13293-024-00673-5 |
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