scholarly journals Regulatory Role of Sex Hormones in Cardiovascular Calcification

2021 ◽  
Vol 22 (9) ◽  
pp. 4620
Author(s):  
Holly J. Woodward ◽  
Dongxing Zhu ◽  
Patrick W. F. Hadoke ◽  
Victoria E. MacRae
Keyword(s):  
Cardiovascular Disease ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Aortic Stenosis ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Increased Risk ◽  
Male Sex ◽  
Primary Male

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

scholarly journals Sex Hormone Regulation of Proteins Modulating Mitochondrial Metabolism, Dynamics and Inter-Organellar Cross Talk in Cardiovascular Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Shannon Lynch ◽  
James E. Boyett ◽  
M. Ryan Smith ◽  
Samantha Giordano-Mooga
Keyword(s):  
Cardiovascular Disease ◽  
Sex Hormones ◽  
Mitochondrial Biogenesis ◽  
Cross Talk ◽  
Mitochondrial Dynamics ◽  
Sex Hormone ◽  
Regulatory Role ◽  
Future Research ◽  
Hormone Regulation

Cardiovascular disease (CVD) is the leading cause of death in the U.S. and worldwide. Sex-related disparities have been identified in the presentation and incidence rate of CVD. Mitochondrial dysfunction plays a role in both the etiology and pathology of CVD. Recent work has suggested that the sex hormones play a role in regulating mitochondrial dynamics, metabolism, and cross talk with other organelles. Specifically, the female sex hormone, estrogen, has both a direct and an indirect role in regulating mitochondrial biogenesis via PGC-1α, dynamics through Opa1, Mfn1, Mfn2, and Drp1, as well as metabolism and redox signaling through the antioxidant response element. Furthermore, data suggests that testosterone is cardioprotective in males and may regulate mitochondrial biogenesis through PGC-1α and dynamics via Mfn1 and Drp1. These cell-signaling hubs are essential in maintaining mitochondrial integrity and cell viability, ultimately impacting CVD survival. PGC-1α also plays a crucial role in inter-organellar cross talk between the mitochondria and other organelles such as the peroxisome. This inter-organellar signaling is an avenue for ameliorating rampant ROS produced by dysregulated mitochondria and for regulating intrinsic apoptosis by modulating intracellular Ca2+ levels through interactions with the endoplasmic reticulum. There is a need for future research on the regulatory role of the sex hormones, particularly testosterone, and their cardioprotective effects. This review hopes to highlight the regulatory role of sex hormones on mitochondrial signaling and their function in the underlying disparities between men and women in CVD.

scholarly journals Sex Hormones and Change in N-Terminal Pro–B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis

2018 ◽  
Vol 103 (11) ◽  
pp. 4304-4314 ◽  
Author(s):  
Wendy Ying ◽  
Di Zhao ◽  
Pamela Ouyang ◽  
Vinita Subramanya ◽  
Dhananjay Vaidya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Sex Differences ◽  
Natriuretic Peptide ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Total Testosterone ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Cross Sectional

Abstract Context Sex hormones may influence sex differences in cardiovascular disease (CVD). N-terminal pro–B-type natriuretic peptide (NT-proBNP), a predictor of CVD, is higher in women than men, which may relate to sex hormones. Objective To evaluate whether total testosterone (T), bioavailable T, free T, estradiol, dehydroepiandrosterone (DHEA), and SHBG are associated with NT-proBNP. Design Cohort study. Participants Cross-sectional sample included 2371 postmenopausal women and 2688 men free of CVD, of which 2041 women and 2348 men were included longitudinally. Main Outcome Measures NT-proBNP at baseline (2000 to 2002) and one or more repeat NT-proBNPs (through 2012). Analyses adjusted for CVD risk factors. Results Women had higher NT-proBNP than men (median 79.9 vs 38.5 pg/mL). Cross-sectionally, higher bioavailable T, free T, DHEA, and lower SHBG levels were independently associated with lower NT-proBNP among both women and men (all P < 0.05). Higher total T in women and estradiol in men were also associated with lower NT-proBNP (both P < 0.05). Longitudinally, in women, higher total T, bioavailable T, free T, DHEA, and lower estradiol and SHBG were associated with greater 10-year increase in NT-proBNP (all P < 0.05). In men, higher free T and estradiol were associated with greater NT-proBNP increase (both P < 0.05). Conclusions A more androgenic sex hormone pattern was inversely associated with NT-proBNP cross-sectionally and may contribute to sex differences in NT-proBNP. Longitudinally, a more androgenic sex hormone pattern was associated with greater increase in NT-proBNP in women, which may reflect a mechanism for CVD risk after menopause.

scholarly journals Sex differences in the intestinal microbiome: interactions with risk factors for atherosclerosis and cardiovascular disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shamon Ahmed ◽  
J. David Spence
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Sex Differences ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Sex Hormones ◽  
Metabolic Profile ◽  
Intestinal Microbiome ◽  
Low Grade

Abstract Background There are clearly sex differences in cardiovascular disease. On average, women experience cardiovascular events at an older age, and at any age, women, on average, have less atherosclerotic plaque than men. The role of the human intestinal microbiome in health and disease has garnered significant interest in recent years, and there have been indications of sex differences in the intestinal microbiome. The purpose of this narrative review was to evaluate evidence of sex differences in the interaction between the intestinal microbiome and risk factors for cardiovascular disease. Several studies have demonstrated changes in microbiota composition and metabolic profile as a function of diet, sex hormones, and host metabolism, among other factors. This dysbiosis has consequently been associated with several disease states, including atherosclerosis and cardiovascular disease. In this respect, there is a growing appreciation for the microbiota and its secreted metabolites, including trimethylamine N-oxide (TMAO), derived from intestinal bacterial metabolic pathways involving dietary choline and l-carnitine, as novel risk factors for atherosclerosis and cardiovascular outcomes. Although traditional risk factors for vascular disease have been studied broadly over the years, there exists little research to evaluate interactions of cardiovascular risk factors with a potentially sexually dimorphic intestinal microbiome. This review evaluates the role of sex differences in the composition of the intestinal microbiome, including effects of sex hormones on the microbiome, and the effects of these sex differences on cardiovascular risk factors. Diabetes and obesity exhibit sexual dimorphism, while the data concerning hypertension and dyslipidemia remain inconclusive based on the available literature. In addition, an increased proportion of gram-negative species capable of driving metabolic endotoxemia and a low-grade inflammatory response, as well as decreased numbers of butyrate-producing species, have been observed in relation to traditional vascular risk factors. In this context, circulating SCFAs and TMAO are recognized as key metabolites of the intestinal microbiome that can be readily measured in the blood for the evaluation of metabolic profile. Conclusion Novel strategies focused on resolving intestinal dysbiosis as a means to slow progression of atherosclerosis and reduce the risk of cardiovascular disease should be evaluated through a lens of sex differences.

Sex differences in transaortic flow rate and association with all-cause mortality in patients with severe aortic stenosis

2021 ◽  
Author(s):  
Sahrai Saeed ◽  
Anastasia Vamvakidou ◽  
Spyridon Zidros ◽  
George Papasozomenos ◽  
Vegard Lysne ◽  
...  
Keyword(s):  
Sex Differences ◽  
Aortic Stenosis ◽  
Flow Rate ◽  
Cox Regression ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P < 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P < 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P < 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.

scholarly journals COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

2021 ◽  
Vol 36 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Joshua Elliott ◽  
Barbara Bodinier ◽  
Matthew Whitaker ◽  
Cyrille Delpierre ◽  
Roel Vermeulen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Vitamin D ◽  
Regression Models ◽  
Oral Steroid ◽  
Uk Biobank ◽  
Steroid Use ◽  
Increased Risk ◽  
Male Sex

AbstractMost studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

Virtual screening attributes male biased COVID-19 mortality to predicted antiviral activity of female sex hormones

2021 ◽  
Vol 18 ◽  
Author(s):  
Galal Yahya ◽  
Basem Mansour ◽  
Kristina Keuper ◽  
Moataz Shaldam ◽  
Ahmed El-Baz
Keyword(s):  
Virtual Screening ◽  
Sex Hormones ◽  
Hospital Admissions ◽  
Epidemiological Data ◽  
Antiviral Effect ◽  
Sex Hormone ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Disaggregated Data ◽  
Male Sex

Background: Coronavirus disease-19 (COVID-19) is a newly emerged pandemic leading to a state of international alert with millions of infected individuals and thousands of deaths all over the world. Analysis of statistics and epidemiological data for the pandemic outcome pinpointed a puzzling influence of human sex on the heterogeneous outcome of COVID-19, where hospital admissions and mortality were higher among males than females. Two theories explained the observed male-biased COVID-19 mortality based on either dosage of immunoregulatory genes coded in X- chromosomes or on the abundance of the angiotensin-converting enzyme two (ACE2) receptors in males than females. Objective: In our study, we propose a third scenario through virtual screening of direct antiviral effects of sex hormones. Materials & Methods: Updated screening statistics from 47 countries displaying sex-disaggregated data on COVID-19 were employed and visualized in the form of heatmaps depicting sex difference effects on statistics of cases and deaths. Molecular docking and binding simulations of investigated sex steroids against COVID-19 specific proteins were investigated. Results: Analysis of COVID-19 sex-disaggregated data confirmed that male-biased mortality and computer-aided docking found unexpected female sex hormones biased binding against key targets implicated in the life cycle of COVID-19 compared to the male sex hormone testosterone. Other investigated steroids showed promising docking scores, while the male sex hormone exhibited the lowest affinity. Conclusion: Female sex hormones virtually exhibited direct COVID-19 effect. The proposed antiviral effect of sex hormones should be considered to explain the outcomes of mortality; moreover, the fluctuation of sex hormones influences sex and personal derived-differential response to COVID-19 infection.

scholarly journals Association between Risk Factors for Vascular Dementia and Adiponectin

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Juhyun Song ◽  
Won Taek Lee ◽  
Kyung Ah Park ◽  
Jong Eun Lee
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Signal Transduction ◽  
Vascular Dementia ◽  
Case Control ◽  
Case Control Studies ◽  
Insulin Signal Transduction ◽  
Increased Risk ◽  
The Brain

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

scholarly journals Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Binaya Wasti ◽  
Zhifeng Chen ◽  
Yi Ke ◽  
Wen Tao Duan ◽  
Shao-Kun Liu ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Sex Hormones ◽  
Human Body ◽  
Therapeutic Potential ◽  
Corticosteroid Treatment ◽  
Sex Hormone ◽  
Asthma Prevalence ◽  
Term Survival

Sex hormone has become a “hot topic” to evaluate the hormonal therapeutic potential in severe asthma. Th17 cell is one of the main influencing factors involved in the pathogenesis of severe asthma, hence also called as kernel of severe asthma, and Th17 subtype of non-T2 asthma is less responsive (resistance) to inhaled corticosteroid (ICS), so severe in nature. Methyl-CpG binding domain protein 2 (MBD2) is overexpressed and regulates the Th17 differentiation, showing the possibility of therapeutic target in treating Th17 mediated severe asthma. Sex hormone fluctuates at the different physiobiological conditions of the human body and affects the asthma pathobiology showing its role in asthma prevalence, severity, remission, and therapy. This review briefly overviews the sex hormones, their influence in asthma at the different physiobiological conditions of human body, and MBD2 severe asthma connection with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma. Male sex hormone tends to show a beneficial effect and possibly downregulates the expression of Th17 cells via regulating MBD2 through a mechanism distinct from corticosteroid treatment and guides us towards discovery of new therapeutic agent, reduces the asthma-related complications, and promotes long-term survival by lowering the risk of therapy-resistant issues of old age severe asthma.

scholarly journals The Role of Fetuin-A in Disease Processes Prevalent in Postmenopausal Women (El papel de la fetuina A en los procesos de enfermedad prevalentes en mujeres posmenopáusicas)

Retos ◽  
2015 ◽  
pp. 172-179
Author(s):  
Annie A. Bane ◽  
Peter W. Grandjean
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Postmenopausal Women ◽  
Abdominal Fat ◽  
Mineral Density ◽  
Fetuin A ◽  
Increased Risk ◽  
Resistencia A La Insulina ◽  
Low Levels

The purpose of this review is to summarize the role of fetuin-A in disease processes prevalent in postmenopausal women and synthesize effective interventions in obtaining healthy fetuin-A levels. A review of databases for articles related to fetuin-A and diseases associated with postmenopausal women was conducted. Articles were limited to full-text access, published in English since 1944. High fetuin-A levels are closely associated with decreased bone mineral density, increased cardiovascular disease risks, impairment of insulin signaling and disruption of adipocyte functioning. Postmenopausal women have increased risk of osteoporosis, cardiovascular disease, insulin-resistance, intra-abdominal fat accumulation and vascular calcification. Low-levels of fetuin-A have been shown to be protective against the latter. The role of fetuin-A is multi-factorial and the mechanisms in which it is involved in each of these processes are vast. The present body of literature is inconsistent in defining high versus low levels of fetuin-A and their association with healthy-matched controls. The diseases associated with high levels of fetuin-A mimic diseases most prevalent in postmenopausal women. In addition, there is no research, to date, exploring fetuin-A levels in postmenopausal women and the associations it may or may not have in related diseases.Key words: fetuin-A; Alpha2-Heremans-Schmid glycoprotein; cardiovascular disease; and elderly, insulin-resistance, intra-abdominal fat, metabolic syndrome, exercise, weight-loss, calorie restriction and postmenopausal.Resumen. El propósito de esta revisión es sintetizar el papel de la fetuina A en los procesos de enfermedad prevalentes en mujeres posmenopáusicas y resumir las intervenciones efectivas que permiten obtener niveles saludables de fetuina A. Para ello, se revisaron bases de datos con artículos relacionados con fetuina A y las enfermedades asociadas con mujeres posmenopáusicas. La búsqueda de artículos se limitó a aquellos de texto completo publicados en el idioma inglés desde el año 1944. Se encontró que altos niveles de fetuina A están íntimamente relacionados con una reducción de la densidad mineral ósea, un aumento en el riesgo de enfermedad cardiovascular, deterioro de la señalización de la insulina y la alteración del funcionamiento de los adipocitos. Las mujeres posmenopáusicas tienen un mayor riesgo de osteoporosis, enfermedad cardiovascular, resistencia a la insulina, acumulación de grasa intra abdominal y calcificación vascular. Se ha demostrado que niveles bajos de fetuina A son protectores contra esta última condición. El papel de fetuina A es multifactorial y los mecanismos en los que está involucrado en cada uno de estos procesos son muy amplios. El estado actual de la literatura no es consistente en la definición de niveles de fetuina A altos versus bajos y su asociación con controles sanos. Las enfermedades asociadas con altos niveles de fetuina A asemejan las enfermedades más prevalentes en mujeres posmenopáusicas. Además, no existen investigaciones, hasta la fecha, en las que se   exploren los niveles de fetuina A en mujeres posmenopáusicas y las asociaciones que puede o no puede tener en las enfermedades relacionadas.Palabras claves: fetuina A, glicoproteína Alpha2-Heremans-Schmid, enfermedad cardiovascular, adulto mayor, resistencia a la insulina, grasa intra abdominal, síndrome metabólico, ejercicio, pérdida de peso, restricción calórica, posmenopausia.

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