This review presents the dualism between gonadal sex and genetic sex in experimental atherosclerosis, discussing molecular mechanisms driving changes in lipid metabolism, immuno-inflammatory reactivity, and vascular response that affect atherosclerosis progression.
Key Findings
Background
Women have decreased cardiovascular risk compared to men at least until menopause, but the molecular mechanisms beyond this difference are debated.
Epidemiological data and interventional studies with hormone replacement therapy support the observation of reduced cardiovascular risk in premenopausal women.
The molecular mechanisms explaining sex differences in cardiovascular disease remain under active investigation.
Menopause appears to be a key transition point after which the female cardiovascular protection diminishes.
Background
Activation of the estrogen receptor has been shown to be atheroprotective in experimental models of atherosclerosis.
Investigation in experimental models of atherosclerosis has been 'pivotal to prove that the activation of the estrogen receptor is atheroprotective.'
Estrogen receptor activation alone is 'not enough to explain the differences reported in cardiovascular disease between male and female.'
This insufficiency of gonadal sex hormones to fully explain sex differences casts the need to investigate genetic sex contributions.
Background
Sex chromosome complement (genetic sex) contributes to atherosclerosis beyond the contribution of sex hormones (gonadal sex).
The paper frames a 'dualism between gonadal sex and genetic sex' as a key conceptual framework for understanding cardiovascular sex differences.
Genetic sex refers to the sex chromosome complement, while gonadal sex refers to the hormonal contribution.
Both components are presented as necessary to fully explain sex differences in atherosclerosis progression.
Background
Lipid metabolism, immuno-inflammatory reactivity, and vascular response differ between males and females in ways that affect atherosclerosis progression.
Molecular mechanisms driving changes in all three of these biological domains — lipid metabolism, immuno-inflammatory reactivity, and vascular response — are discussed in the context of sex differences.
These mechanisms are presented as collectively contributing to differential atherosclerosis progression between sexes.
The review integrates data from experimental models to characterize these pathways.
Nour J, Bonacina F, Norata G. (2023). Gonadal sex vs genetic sex in experimental atherosclerosis.. Atherosclerosis. https://doi.org/10.1016/j.atherosclerosis.2023.117277