scholarly journals Cardiac GRK2 Protein Levels Show Sexual Dimorphism during Aging and are Regulated by Ovarian Hormones

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 673
Author(s):  
Alba C. Arcones ◽  
Melanie Raquel Martínez-Cignoni ◽  
Rocío Vila-Bedmar ◽  
Claudia Yáñez ◽  
Isabel Lladó ◽  
...  

Cardiovascular disease (CVD) risk shows a clear sexual dimorphism with age, with a lower incidence in young women compared to age-matched men. However, this protection is lost after menopause. We demonstrate that sex-biased sensitivity to the development of CVD with age runs in parallel with changes in G protein-coupled receptor kinase 2 (GRK2) protein levels in the murine heart and that mitochondrial fusion markers, related to mitochondrial functionality and cardiac health, inversely correlate with GRK2. Young female mice display lower amounts of cardiac GRK2 protein compared to age-matched males, whereas GRK2 is upregulated with age specifically in female hearts. Such an increase in GRK2 seems to be specific to the cardiac muscle since a different pattern is found in the skeletal muscles of aging females. Changes in the cardiac GRK2 protein do not seem to rely on transcriptional modulation since adrbk1 mRNA does not change with age and no differences are found between sexes. Global changes in proteasomal or autophagic machinery (known regulators of GRK2 dosage) do not seem to correlate with the observed GRK2 dynamics. Interestingly, cardiac GRK2 upregulation in aging females is recapitulated by ovariectomy and can be partially reversed by estrogen supplementation, while this does not occur in the skeletal muscle. Our data indicate an unforeseen role for ovarian hormones in the regulation of GRK2 protein levels in the cardiac muscle which correlates with the sex-dependent dynamics of CVD risk, and might have interesting therapeutic applications, particularly for post-menopausal women.

2018 ◽  
Vol 50 (5S) ◽  
pp. 225-226
Author(s):  
Maria A. Cardenas ◽  
Michael M. Levitt ◽  
Bryan Richie ◽  
Shaohan Lu ◽  
Elise E. Erickson ◽  
...  

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Jordi Mayneris-Perxachs ◽  
María Arnoriaga-Rodríguez ◽  
Diego Luque-Córdoba ◽  
Feliciano Priego-Capote ◽  
Vicente Pérez-Brocal ◽  
...  

Abstract Background Gonadal steroid hormones have been suggested as the underlying mechanism responsible for the sexual dimorphism observed in metabolic diseases. Animal studies have also evidenced a causal role of the gut microbiome and metabolic health. However, the role of sexual dimorphism in the gut microbiota and the potential role of the microbiome in influencing sex steroid hormones and shaping sexually dimorphic susceptibility to disease have been largely overlooked. Although there is some evidence of sex-specific differences in the gut microbiota diversity, composition, and functionality, the results are inconsistent. Importantly, most of these studies have not taken into account the gonadal steroid status. Therefore, we investigated the gut microbiome composition and functionality in relation to sex, menopausal status, and circulating sex steroids. Results No significant differences were found in alpha diversity indices among pre- and post-menopausal women and men, but beta diversity differed among groups. The gut microbiota from post-menopausal women was more similar to men than to pre-menopausal women. Metagenome functional analyses revealed no significant differences between post-menopausal women and men. Gonadal steroids were specifically associated with these differences. Hence, the gut microbiota of pre-menopausal women was more enriched in genes from the steroid biosynthesis and degradation pathways, with the former having the strongest fold change among all associated pathways. Microbial steroid pathways also had significant associations with the plasma levels of testosterone and progesterone. In addition, a specific microbiome signature was able to predict the circulating testosterone levels at baseline and after 1-year follow-up. In addition, this microbiome signature could be transmitted from humans to antibiotic-induced microbiome-depleted male mice, being able to predict donor’s testosterone levels 4 weeks later, implying that the microbiota profile of the recipient mouse was influenced by the donor’s gender. Finally, obesity eliminated most of the differences observed among non-obese pre-menopausal women, post-menopausal women, and men in the gut microbiota composition (Bray-Curtis and weighted unifrac beta diversity), functionality, and the gonadal steroid status. Conclusions The present findings evidence clear differences in the gut microbial composition and functionality between men and women, which is eliminated by both menopausal and obesity status. We also reveal a tight link between the gut microbiota composition and the circulating levels of gonadal steroids, particularly testosterone.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Vinita Subramanya ◽  
Di Zhao ◽  
Pamela Ouyang ◽  
Wendy Ying ◽  
Dhananjay Vaidya ◽  
...  

Background: Cardiovascular disease (CVD) is the leading cause of death in women. Sex differences in risk factors, prevalence and mortality suggest the involvement of sex hormones in disease processes. Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and its progression. CAC is prognostic of CVD risk, independent of traditional risk factors, even among low-risk women. We hypothesized that a more androgenic hormone pattern will predict CAC progression over 10 years in post-menopausal women. Methods: We studied 2759 post-menopausal women, aged 45-84 years, participating in MESA who underwent serum sex hormone measurement and a cardiac CT scan for CAC at baseline (2000-2002). Among these, 2427 women had up to 3 follow-up cardiac CT scans at subsequent visits spanning 10 years. CAC was assessed by Agatson units. CAC and sex hormones were log-transformed for analysis. Using multivariable-adjusted Poisson and linear mixed effects models, we tested the longitudinal associations of testosterone (T), free T, dehydroepiandrosterone (DHEA), estradiol (E2), and sex hormone binding globulin (SHBG) with prevalent CAC and progression of CAC over 10 years. Results: At baseline, average age was 65 years, 46% had prevalent CAC and 32% were using hormone therapy (HT). Cross-sectionally, there were no associations between sex hormones and prevalent CAC. After adjustment for demographics, lifestyle factors and use of HT, higher levels of free T and lower levels of SHBG were associated with an increase in CAC progression over 10 years ( Table, Model 2). These associations remained statistically significant after adjusting for potential mediating cardiovascular risk factors (Model 3) and in sensitivity analyses excluding women on HT. Conclusion: A more androgenic hormone profile of higher free T and lower SHBG is associated with a greater CAC progression over 10 years in post-menopausal women. Sex hormone levels may help identify women at increased CVD risk who may benefit from other risk reduction strategies.


2010 ◽  
Vol 120 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Gary L. Pierce ◽  
Iratxe Eskurza ◽  
Ashley E. Walker ◽  
Tara N. Fay ◽  
Douglas R. Seals

Brachial artery FMD (flow-mediated dilation) is impaired with aging and is associated with an increased risk of CVD (cardiovascular disease). In the present study, we determined whether regular aerobic exercise improves brachial artery FMD in MA/O (middle-aged/older) men and post-menopausal women. In sedentary MA/O adults (age, 55–79 years) without CVD, 8 weeks of brisk walking (6 days/week for approx. 50 min/day; randomized controlled design) increased treadmill time approx. 20% in both MA/O men (n=11) and post-menopausal women (n=15) (P<0.01), without altering body composition or circulating CVD risk factors. Brachial artery FMD increased >50% in the MA/O men (from 4.6±0.6 to 7.1±0.6%; P<0.01), but did not change in the post-menopausal women (5.1±0.8 compared with 5.4±0.7%; P=0.50). No changes occurred in the non-exercising controls. In a separate cross-sectional study (n=167), brachial artery FMD was approx. 50% greater in endurance-exercise-trained (6.4±0.4%; n=45) compared with sedentary (4.3±0.3%; n=60) MA/O men (P<0.001), whereas there were no differences between endurance-trained (5.3±0.7%, n=20) and sedentary (5.6±0.5%, n=42) post-menopausal women (P=0.70). Brachial artery lumen diameter, peak hyperaemic shear rate and endothelium-independent dilation did not differ with exercise intervention or in the endurance exercise compared with sedentary groups. In conclusion, regular aerobic exercise is consistently associated with enhanced brachial artery FMD in MA/O men, but not in post-menopausal women. Some post-menopausal women without CVD may be less responsive to habitual aerobic exercise than MA/O men.


2021 ◽  
Vol 9 (2) ◽  
pp. 112-115
Author(s):  
D. Jayarajan ◽  
V. Abirami

Pre and post menopause were the complications faced by women globally that not only interferes in physical health but also in mental health of a woman. The menopause factors includes many traditional CVD risk factors, including changes in body fat distribution from agynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation . Menopause is a risk factor for (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism .The present study aimed for inflammatory markers of cardio metabolic risk factors in post menopausal women and premenopausal women and the results recorded the significant level of elevation in all parameters compared with case and control samples and the significance was given as student’s t test(p&#60;0.001).


2020 ◽  
Author(s):  
Kyu-Min Park ◽  
Seung-Taek Lim ◽  
Kun-Young Sung ◽  
Sunghwun Kang

Abstract Background and objectives: The purpose of study was to examine the effects of regular resistance exercise for 12 weeks on lipolysis pathway in pre- and post- menopausal women with obesity. Methods: Twenty-three pre- and post- menopausal women with body fat percentages of 30% or more divided into pre- menopausal group (n=9) and post- menopausal group (n=14). All subjects participated in resistance exercise training for 12 weeks. Anthropometric and physical fitness tests were performed on all participants. Protein analyses were performed with subcutaneous fatty tissue extracted, and the samples were analyzed of relevant protein levels changes by using Western blotting. All serum samples were submitted for enzyme-linked immunosorbent assay measurements of adipocyte factors. Results: After 12 weeks between pre- menopausal and post- menopausal groups adipose triglyceride lipase (ATGL), monoacylglycerol lipase (MGL) and perilipin (PLIN) protein levels were significantly lower in the post- menopausal group than in the pre- menopausal group. Hormone-sensitive lipase (HSL) protein levels were significantly higher in the post- menopausal group than in the pre- menopausal group. In addition, leptin concentration was significantly decreased after resistance exercise in the post- menopausal group. Adiponectin concentration was significantly increased after resistance exercise in the both groups. Conclusions: This study indicates that regular resistance exercise to change of leptin and adiponectin might be release of reduction of % fat, and driving overall greater change ATGL, HSL, MGL and PLIN levels in subcutaneous fatty tissue in the obese post- menopausal group more than obese pre- menopausal group.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Lena Mathews ◽  
Vinita Subramanya ◽  
Di Zhao ◽  
Pamela Ouyang ◽  
Dhanajay Vaidya ◽  
...  

Background: Sex is a major determinant of cardiovascular disease (CVD). Endogenous sex hormones exert a variety of effects on the vascular endothelium, and changes in sex hormone levels after menopause may play a role in CVD risk in women. We hypothesized that a more androgenic sex hormone profile among post-menopausal women, but not among men, would be associated with reduced blood flow-mediated vasodilation (FMD) of the brachial artery, a marker of worse endothelial function. Methods: We examined 1396 post-menopausal women and 1707 men participating in MESA, who were free of clinical CVD at baseline. Sex hormone levels [total testosterone (T), sex hormone binding globulin (SHBG), estradiol (E2)] were measured at Exam 1 (2000-02); free T and T/E2 ratio were calculated. FMD was measured by high-resolution ultrasound. Using multivariable adjusted Poisson and linear regression methods, we tested the cross-sectional associations of sex hormones (log transformed) with FMD. Results: The mean age of men and women was 61 and 64 years, respectively. Of women, 34% were using hormone therapy (HT). Among women, after adjusting for demographics, CVD risk factors, and HT use, higher SHBG was associated with higher FMD, whereas higher free T was associated with lower FMD (Table, Model 2). In women, when examining the “best FMD response” (top decile vs. bottom 9 deciles), higher E2 was positively associated with a prevalent best response, whereas higher free T was inversely associated. Among men, a higher T/E2 ratio was marginally associated with lower FMD. Conclusion: The association between sex hormones and FMD differs in men and women. Higher E2 and SHBG and lower free T levels were associated with better FMD in post-menopausal women but not in men. Higher T/E2 ratio was associated with lower FMD in men. Further studies are needed to assess longitudinal changes in sex hormone levels and their association with vascular aging. Sex hormone levels may help identify individuals at increased CVD risk who may benefit from other risk reduction strategies.


2016 ◽  
Vol 53 (2) ◽  
pp. 219
Author(s):  
Shazia Husain ◽  
Vibha Bhatnagar

Osteoporosis and cardiovascular disease (CVD) are a major growing public health problem with impact that crosses medical, social and economic lines. The aim of this study was to assess the prevalence and risk of osteoporosis and CVD in post menopausal women. A cross sectional study was conducted on 322 post menopausal women aged 45-55 years residing in Udaipur city, Rajasthan. Risk of osteoporosis in subjects was assessed using Osteoporosis Self Assessment Tool for Asian (OSTA) and risk of CVD was determined using CVD risk assessment tool. The body weight and age of subjects were calculated for the OSTA index sore. Total cholesterol, high density lipoprotein, diastolic blood pressure and smoking habits of subjects were assessed for CVD risk score. Results of OSTA assessment revealed that 24.22 % respondents were at medium risk of osteoporosis whereas results of CVD assessment showed that a large number of subjects i.e. 82.91 % were at medium risk of CVD. Combining both the assessment scores of subjects, 23.91 % post menopausal women were found at medium risk of both osteoporosis and CVD. Study showed a lower prevalence of osteoporosis having medium risk and higher prevalence of CVD having moderate risk in post menopausal women. The findings suggest that more studies should be done on these at risk population for preventive and therapeutic interventions.


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