Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

Arosio, Beatrice; Corbi, Graziamaria; Davinelli, Sergio; Giordano, Vienna; Liccardo, Daniela; Rapacciuolo, Antonio; Cannavò, Alessandro

doi:10.3390/ijms23074009

Cited by 16 publications

(7 citation statements)

References 195 publications

(241 reference statements)

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“…Similarly, Machuki and coworkers [ 153 ] provided an updated description of Es receptors (ERs) and β-ARs signaling, and their functional synergism in cardiac cells. However, as discussed previously by us and others, these sex hormones are crucially involved in sex differences in CVDs manifestation, clinical outcome, and response to therapy in males and females [ 7 , 8 , 14 , 152 , 153 , 154 ]. Notably, a significant decrease in the levels of these hormones is observed in the postmenopausal period and is considered the primary causal factor for the increased CV risk in women with aging [ 14 ].…”

Section: Impact Of Estrogens and Its Supplementation On β-Ar Signalin...mentioning

confidence: 93%

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Liccardo

Arosio

Corbi

et al. 2022

JCM

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Sex differences in cardiovascular disease (CVD) are often recognized from experimental and clinical studies examining the prevalence, manifestations, and response to therapies. Compared to age-matched men, women tend to have reduced CV risk and a better prognosis in the premenopausal period. However, with menopause, this risk increases exponentially, surpassing that of men. Although several mechanisms have been provided, including sex hormones, an emerging role in these sex differences has been suggested for β-adrenergic receptor (β-AR) signaling. Importantly, β-ARs are the most important G protein-coupled receptors (GPCRs), expressed in almost all the cell types of the CV system, and involved in physiological and pathophysiological processes. Consistent with their role, for decades, βARs have been considered the first targets for rational drug design to fight CVDs. Of note, β-ARs are seemingly associated with different CV outcomes in females compared with males. In addition, even if there is a critical inverse correlation between β-AR responsiveness and aging, it has been reported that gender is crucially involved in this age-related effect. This review will discuss how β-ARs impact the CV risk and response to anti-CVD therapies, also concerning sex and age. Further, we will explore how estrogens impact β-AR signaling in women.

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Section: Impact Of Estrogens and Its Supplementation On β-Ar Signalin...mentioning

confidence: 93%

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Liccardo

Arosio

Corbi

et al. 2022

JCM

Self Cite

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“…Numerous studies have described the effects of sex hormones on cardiovascular cells, organs and disease phenotypes (reviewed previously 19 – 21 ). However, the effects of the physical or sociocultural environment, nutrition, or stress (that is, the effects of gender) were not always excluded in these reports.…”

Section: Biological Sex In Cvdmentioning

confidence: 99%

Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes

Regitz‐Zagrosek

Gebhard

2022

Nat Rev Cardiol

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Despite a growing body of evidence, the distinct contributions of biological sex and the sociocultural dimension of gender to the manifestations and outcomes of ischaemic heart disease and heart failure remain unknown. The intertwining of sex-based differences in genetic and hormonal mechanisms with the complex dimension of gender and its different components and determinants that result in different disease phenotypes in women and men needs to be elucidated. The relative contribution of purely biological factors, such as genes and hormones, to cardiovascular phenotypes and outcomes is not yet fully understood. Increasing awareness of the effects of gender has led to efforts to measure gender in retrospective and prospective clinical studies and the development of gender scores. However, the synergistic or opposing effects of sex and gender on cardiovascular traits and on ischaemic heart disease and heart failure mechanisms have not yet been systematically described. Furthermore, specific considerations of sex-related and gender-related factors in gender dysphoria or in heart–brain interactions and their association with cardiovascular disease are still lacking. In this Review, we summarize contemporary evidence on the distinct effects of sex and gender as well as of their interactions on cardiovascular disease and how they favourably or unfavourably influence the pathogenesis, clinical manifestations and treatment responses in patients with ischaemic heart disease or heart failure.

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“…Some of these sex differences might be attributed to hormonal differences. 32 For instance, estrogen protects blood vessels, in part, by lowering inflammation. Estrogen levels in females drop after menopause thereby potentially increasing the risk of CSVD.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure

Kaur,

Angarita Fonseca,

Lissaman

et al. 2024

Hypertension

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BACKGROUND: Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease–related brain structural changes. METHODS: We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. RESULTS: Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. CONCLUSIONS: Our study demonstrates that the effect of hypertension on cerebral small vessel disease–related brain structure differs by sex and by age at hypertension diagnosis.

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Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

Cited by 16 publications

References 195 publications

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure

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