Why the study?
Outcomes of acute MI differ between sexes, but the impact of sex hormones on mental stress induced ischemia and sympathetic activation remains unknown.
Do sex and sex hormones affect myocardial sympathetic tone and left ventricular remodeling following myocardial injury in an animal model?
Do sex and sex hormones affect myocardial sympathetic tone and left ventricular remodeling following myocardial injury in an animal model?
In a preclinical model of myocardial infarction, testosterone is associated with increased sympathetic tone and adverse cardiac remodeling, suggesting a biological advantage of female sex in post-MI recovery.
Testosterone may drive sympathetic activation and adverse remodeling post-MI in male rodents; hypothesis-generating for sex-specific mechanisms pending human studies.
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: C]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.
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Haider et al. (2025) studied this question.
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