Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury.
Publisher DOI
PubMed ID
39819738
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.Heart attacks affect men and women differently, with younger women often experiencing worse outcomes than men. One reason for this difference might be how stress and heart nerve activity are influenced by sex hormones, though this has not been well understood to date.In this study, we investigated how sex hormones and age affect heart damage and nerve activity in male and female mice. We used advanced imaging techniques to look at the hearts of young and older mice, some of which had their sex organs removed to study the hormone effects.Our results showed that young male mice had higher nerve activity and stress hormone levels after a heart attack compared to young female mice. Removing the male sex hormone (testosterone) reduced this activity, suggesting testosterone worsens heart damage. In contrast, removing female sex hormones (oestrogen and progesterone) did not affect nerve activity in female mice. Females also maintained better heart function after a heart attack, regardless of their hormones.In summary, male sex hormones may worsen early heart attack recovery by increasing stress on the heart, while female hearts were more resilient in our study. This information could help refine risk stratification and treatment of heart attack in men and women.
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.Heart attacks affect men and women differently, with younger women often experiencing worse outcomes than men. One reason for this difference might be how stress and heart nerve activity are influenced by sex hormones, though this has not been well understood to date.In this study, we investigated how sex hormones and age affect heart damage and nerve activity in male and female mice. We used advanced imaging techniques to look at the hearts of young and older mice, some of which had their sex organs removed to study the hormone effects.Our results showed that young male mice had higher nerve activity and stress hormone levels after a heart attack compared to young female mice. Removing the male sex hormone (testosterone) reduced this activity, suggesting testosterone worsens heart damage. In contrast, removing female sex hormones (oestrogen and progesterone) did not affect nerve activity in female mice. Females also maintained better heart function after a heart attack, regardless of their hormones.In summary, male sex hormones may worsen early heart attack recovery by increasing stress on the heart, while female hearts were more resilient in our study. This information could help refine risk stratification and treatment of heart attack in men and women.
Date Issued
2025-01-16
Publication Type
Article
Subject(s)
Subjects
Cardiac magnetic resonance (CMR) imaging
•
Myocardial infarction
•
Positron emission tomography (PET)
•
Sex
•
Sex hormones
•
[11C]meta-hydroxyephedrine
Language(s)
en
Author(s)
Haider, Achi | |
Bengs, Susan | |
Portmann, Angela | |
Fröhlich, Sandro | |
Etter, Dominik | |
Maredziak, Monika | |
Warnock, Geoffrey I | |
Akhmedov, Alexander | |
Kozerke, Sebastian | |
Keller, Claudia | |
Montecucco, Fabrizio | |
Buechel, Ronny R | |
Kaufmann, Philipp A | |
Camici, Giovanni G | |
Ametamey, Simon M |
Additional Credits
Journal
Biology of Sex Differences
Publisher
BioMed Central
ISSN
2042-6410
Access(Rights)
open.access