Sex and gender aspects in vascular pathophysiology

Connelly, Paul; Jandeleit‐Dahm, Karin; Delles, Christian

doi:10.1042/cs20200876

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…This could be indicative of sex-dependent differences in vascular biology, which may have implications for cerebral blood flow, hemodynamics, neurovascular coupling, or other aspects of cerebrovascular health in middle aged mice. 17,46,[69][70][71] Whether the measured differences translate to hemodynamic differences in these mice is currently unknown. In prior published studies of young mice, as well as humans, females have been shown to have higher cerebral blood flow than males, but this flow declines more rapidly with age in females.…”

Section: Discussionmentioning

confidence: 99%

Using digital pathology to analyze the murine cerebrovasculature

Niedowicz,

Gollihue,

Weekman

et al. 2023

J Cereb Blood Flow Metab

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Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and cross-reactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed sections. A panel of immunohistochemical blood vessel markers were tested (including CD31, CD34, collagen IV, DP71, and VWF), to evaluate their suitability for digital pathological analysis. Collagen IV provided the best immunostaining results in both FFPE and frozen fixed murine brain sections, with highly-specific staining of large and small blood vessels and low background staining. Subsequent analysis of collagen IV-stained sections showed region and sex-specific differences in vessel density and vessel wall thickness. We conclude that digital pathology provides a useful tool for relatively unbiased analysis of the murine cerebrovasculature, provided proper protein markers are used.

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Section: Discussionmentioning

confidence: 99%

Using digital pathology to analyze the murine cerebrovasculature

Niedowicz,

Gollihue,

Weekman

et al. 2023

J Cereb Blood Flow Metab

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“…Sex hormones, including estrogen, progesterone, and testosterone, play significant roles in cardiovascular health and disease ( 29 , 30 ). Estrogen, primarily found in premenopausal women, exerts cardioprotective effects ( 8 , 29 , 31 ). It helps maintain healthy blood vessel function by promoting vasodilation, reducing inflammation, and inhibiting the formation of atherosclerotic plaques.…”

Section: Sex Hormones In Cvdmentioning

confidence: 99%

“…Within cardiovascular medicine, sex and gender affect disease presentation, pathophysiology, diagnostic assessment, responses to treatments, and overall health outcomes ( 6 , 7 ). Historically, CVD has been perceived as primarily affecting men; however, it is increasingly recognized as a leading cause of morbidity and mortality in women as well ( 8 ). While men tend to develop CVD earlier in life, CVD prevalence increases significantly in postmenopausal women, narrowing the gap between the sexes ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Editorial: Sex differences and cardiovascular therapeutics

Saaoud,

Xu,

et al. 2024

Front. Cardiovasc. Med.

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“…Socioeconomic factors such as age, partnered status, access to a stable social network and intimate social support (ie. with a partner, family, close friends), income, and education/vocation all have wellestablished epidemiological associations with risk of depression and IHD (Connelly et al, 2020).…”

Section: Limitationsmentioning

confidence: 99%

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Théberge

Dennis

2023

Preprint

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Major depressive disorder (MDD) is a leading cause of morbidity and disability worldwide, with approximately twice as many women reported to have a lifetime occurrence of MDD than men. MDD is a polygenic trait, wherein hundreds to thousands of common genetic variants with small effect sizes contribute to risk of disease. This study investigated sex differences in the risk factor comorbidity and genetic architecture of MDD in over 16,000 people aged 45-85 from the Canadian Longitudinal Study on Aging (CLSA), with 21% of females (n=1,741) and 12% of males (n=1,055) coded with MDD. Polygenic risk scores (PRS) for individuals were made using sex-stratified and non-sex-specific ("both-sexes") UK Biobank genome-wide association study summary statistics data. Odds of MDD for the sex-specific PRSs, socioeconomic, lifestyle and clinical risk factors associated with cardiovascular disease risk were assessed using a multivariable logistic regression model for each sex. Significant sex-specific risk factor associations with odds of MDD were found in females (history of ischemic heart disease (OR 1.52 (1.14-2.01), hypothyroidism (OR 1.42 (1.25-1.63), not being partnered (OR 1.34 (1.17-1.52)), having diabetes (OR 1.30 (1.11-1.52)), and higher female sex-specific autosomal PRS (OR 1.10 (1.04-1.16))) and males (high blood pressure, OR 1.35 (1.04-1.47)). Significant differences were observed in the proportion of variables that contributed to the most to each model, evaluated by relative pseudo-R2 values. Age contributed the most to the model for both sexes (46.9% for females, 32.5% for males), wherein younger age was associated with higher odds of MDD. These results underscore the relevance for sex-disaggregating analyses of complex traits, like MDD, and the incorporation of clinical variables into models of MDD, in applications such as early detection and primary prevention.

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Sex and gender aspects in vascular pathophysiology

Cited by 4 publications

References 42 publications

Using digital pathology to analyze the murine cerebrovasculature

Using digital pathology to analyze the murine cerebrovasculature

Editorial: Sex differences and cardiovascular therapeutics

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

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