An emerging perspective on sex differences: Intersecting S-nitrosothiol and aldehyde signaling in the heart.
Ontology highlight
ABSTRACT:
SUBMITTER: Casin KM
PROVIDER: S-EPMC7212482 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
An emerging perspective on sex differences: Intersecting S-nitrosothiol and aldehyde signaling in the heart.
Casin Kevin M KM Kohr Mark J MJ
Redox biology 20200125
Cardiovascular disease is the leading cause of the death for both men and women. Although baseline heart physiology and the response to disease are known to differ by sex, little is known about sex differences in baseline molecular signaling, especially with regard to redox biology. In this review, we describe current research on sex differences in cardiac redox biology with a focus on the regulation of nitric oxide and aldehyde signaling. Furthermore, we argue for a new perspective on cardiovas ...[more]
Similar Datasets
Project description:This in-depth review of sex differences in advanced heart failure therapy summarizes the existing literature on implantable cardioverter defibrillators, biventricular pacemakers, mechanical circulatory support, and transplantation with a focus on utilization, efficacy/clinical effectiveness, adverse events, and controversies. One will learn about the controversies regarding efficacy/clinical effectiveness of implantable cardioverter defibrillators and understand why these devices should be implanted in women even if there are sex differences in appropriate shocks. Individuals will learn about the sex differences with biventricular pacemakers with respect to ventricular remodeling and reduction in heart failure hospitalizations/mortality, as well as, possible mechanisms. We will demonstrate sex differences in heart transplantation and waitlist survival. Despite similar survival for women and men with left ventricular assist devices, there are sex differences in adverse events. These devices do successfully bridge women and men to transplant, yet women are less likely than men to have a left ventricular assist at time of listing and time of transplantation. Finally, one will learn about the concerns regarding poor outcome for men who receive female donor hearts and discover this may not be due to sex, but rather size. More research is needed to better understand sex differences and further improve advanced heart failure therapy for both women and men.
| S-EPMC6383806 | biostudies-literature
Project description:Premenopausal women exhibit endogenous cardioprotective signaling mechanisms that are thought to result from the beneficial effects of estrogen, which we have shown to increase protein S-nitrosylation in the heart. S-nitrosylation is a labile protein modification that increases with a number of different forms of cardioprotection, including ischemic preconditioning. Herein, we sought to identify a potential role for protein S-nitrosylation in sex-dependent cardioprotection. We utilized a Langendorff-perfused mouse heart model of ischemia-reperfusion injury with male and female hearts, and S-nitrosylation-resin-assisted capture with liquid chromatography tandem mass spectrometry to identify S-nitrosylated proteins and modification sites. Consistent with previous studies, female hearts exhibited resilience to injury with a significant increase in functional recovery compared with male hearts. In a separate set of hearts, we identified a total of 177 S-nitrosylated proteins in female hearts at baseline compared with 109 S-nitrosylated proteins in male hearts. Unique S-nitrosylated proteins in the female group included the F1FO-ATPase and cyclophilin D. We also utilized label-free peptide analysis to quantify levels of common S-nitrosylated identifications and noted that the S-nitrosylation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2a was nearly 70% lower in male hearts compared with female, with no difference in expression. Furthermore, we found a significant increase in endothelial nitric oxide synthase expression, phosphorylation, and total nitric oxide production in female hearts compared with males, likely accounting for the enhanced S-nitrosylation protein levels in female hearts. In conclusion, we identified a number of novel S-nitrosylated proteins in female hearts that are likely to contribute to sex-dependent cardioprotection.
| S-EPMC4796614 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesize that mitochondrial sex differences might underlie this bias. As part of genetic studies of heart failure in mice, we observe that heart mitochondrial DNA levels and function tend to be reduced in females as compared to males. We also observe that expression of genes encoding mitochondrial proteins are higher in males than females in human cohorts. We test our hypothesis in a panel of genetically diverse inbred strains of mice, termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, we find that mitochondrial gene expression is highly correlated with diastolic function, a key trait in HFpEF. Consistent with this, studies of a "two-hit" mouse model of HFpEF confirm that mitochondrial function differs between sexes and is strongly associated with a number of HFpEF traits. By integrating data from human heart failure and the mouse HMDP cohort, we identify the mitochondrial gene Acsl6 as a genetic determinant of diastolic function. We validate its role in HFpEF using adenoviral over-expression in the heart. We conclude that sex differences in mitochondrial function underlie, in part, the sex bias in diastolic function.
| S-EPMC9253085 | biostudies-literature
Project description:We aimed to characterize patterns of differences in heart graft failure rates by recipient sex, accounting for modifying effects of donor sex and recipient age.MethodsWe evaluated 69 246 first heart transplant recipients (1988-2019; Scientific Registry of Transplant Recipients). We used multivariable time-varying Cox models, considering recipient sex by donor sex by recipient age interaction and adjusting for potential confounders. Using the hazard ratio (HR) from the models and a fixed profile of recipient and donor characteristics, we also compared fitted absolute failure rates by recipient sex.ResultsAmong recipients of male donors, female recipients of all ages had higher failure rates than males (0-12 y: HR 1.36 (95% confidence interval [CI], 1.03-1.81); 13-24 y: 1.43 [1.09-1.88]; 25-44 y: 1.22 [0.95-1.57]; ≥45 y: 1.16 [1.06-1.27]); differences were statistically significant in all age intervals except 25-44 y. When the donor was male, 13 to 24-y-olds showed the largest absolute difference in fitted absolute failure rates, with rates higher by 11.3 failures per 1000 person-y in female than male recipients. Among recipients of female donors, there were no statistically significant differences in graft failure rates between female and male heart recipients of any age. Although point estimates suggested higher failure rates in female than male recipients <25 y (0-12 y: HR 1.19 [95% CI, 0.85-1.66]; 13-24 y: 1.17 [0.84-1.63]), these were not statistically significant.ConclusionsFemale recipients tended to have poorer outcomes than males, particularly at younger ages and when the donor was male, consistent with observations in kidney transplants.
| S-EPMC8425832 | biostudies-literature
Project description:BackgroundSagittal abdominal diameter (SAD) is an anthropometric index associated with visceral adiposity. It remains unclear whether SAD and its socio-economic correlates differ in women and men, which limits the epidemiological and clinical applications of the SAD measurement. The aims of this study are to examine the sex differences in SAD and its socio-economic correlates.MethodsA complex stratified multistage clustered sampling design was used to select 6975 men and 7079 women aged 18 years or more from the National Health Nutrition and Examination Survey 2011-2016, representative of the US civilian non-institutionalized population. SAD was measured in accordance to the standard protocols using a two-arm abdominal caliper. The sex differences in SAD and its socio-economic correlates were evaluated by performing weighted independent t tests and weighted multiple regression.ResultsSAD was lower in women than in men in the entire sample, as well as in all the subgroups characterized by age, race, birth place, household income, and body mass index except for non-Hispanic blacks and those with household income < $20,000. Adjusted for other characteristics, age, birth place, household income, and body mass index were associated with SAD in both women and men. Black women were associated with higher SAD then white women (p < .0001), and Hispanic and Asian men were associated with lower SAD than white men (both p < .01). Women born in other countries were more likely to have lower SAD than women born in the US (p < .0001), and so were men (p = .0118). Both women and men with a household income of <$75,000 had higher SAD than those with an income of over $75,000. The associations of age, race, and household income with SAD differed in women and men.ConclusionSAD is lower in women than in men, in the general population as well as in the most socio-economic subgroups. While socio-economic correlates of SAD are similar in women and men, the associations of age, race, and household income with SAD vary across sex.
| S-EPMC7953618 | biostudies-literature
Project description:S-Nitrosothiols (RSNOs) serve as air-stable reservoirs for nitric oxide in biology. While copper enzymes promote NO release from RSNOs by serving as Lewis acids for intramolecular electron-transfer, redox-innocent Lewis acids separate these two functions to reveal the effect of coordination on structure and reactivity. The synthetic Lewis acid B(C6 F5 )3 coordinates to the RSNO oxygen atom, leading to profound changes in the RSNO electronic structure and reactivity. Although RSNOs possess relatively negative reduction potentials, B(C6 F5 )3 coordination increases their reduction potential by over 1 V into the physiologically accessible +0.1 V vs. NHE. Outer-sphere chemical reduction gives the Lewis acid stabilized hyponitrite dianion trans-[LA-O-N=N-O-LA]2- [LA=B(C6 F5 )3 ], which releases N2 O upon acidification. Mechanistic and computational studies support initial reduction to the [RSNO-B(C6 F5 )3 ] radical anion, which is susceptible to N-N coupling prior to loss of RSSR.
| S-EPMC7385465 | biostudies-literature
Project description:Sex differences are known in several facets of cardiac electrophysiology, mostly concerning myocardial repolarisation. In this study, heart rate and heart rate variability (HRV) responses to postural provocations were compared in 175 and 176 healthy females and males, respectively (aged 33.1?±?9.1 years). Two different postural provocative tests with position changes supine?sitting?standing?supine and supine?standing?sitting?supine (15-min standing, 10-min other positions) were performed up to 4 times in each subject. Heart rate and heart rate variability spectral indices were measured in 5-min windows before positional changes. At supine position, females had averaged heart rate approximately 5 beats per minute (bpm) faster than males and this sex difference was practically constant during the postural changes. In both sexes, change supine?sitting and supine?standing increased heart rate by approximately 10 and 30 bpm, respectively, with no statistical differences between the sex groups. At supine baseline, females had normalised high frequency components (nHF) of HRV approximately 7% larger compared to males (p?<?0.001). While the same difference in nHF was found at sitting, the change to standing position lead to significantly larger nHF reduction in females compared to males (mean changes 22.5 vs 17.2%, p?<?0.001). This shows that despite similar heart rate increase, females respond to standing by more substantial shifts in cardiac sympatho-vagal modulations. This makes it plausible to speculate that the differences in autonomic reactions to stress contribute to the known sex-differences in psychosocial responses to stressful situations and to the known difference in susceptibility to ventricular fibrillation between females and males.
| S-EPMC6926477 | biostudies-literature
Project description:Background The female preponderance in heart failure with preserved ejection fraction (HFpEF) is a distinguishing feature of this disorder, but the association of sex with degree of diastolic dysfunction and clinical outcomes among individuals with HFpEF remains unclear. Methods and Results We conducted a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF [Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction]: UMIN000021831). Between 2016 and 2019, 871 patients were enrolled from 26 hospitals (follow-up: 399±349 days). We investigated sex-related differences in diastolic dysfunction and postdischarge clinical outcomes in patients with HFpEF. The echocardiographic end point was diastolic dysfunction according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. The clinical end point was a composite of all-cause death and heart failure readmission. Women accounted for 55.2% (481 patients) of the overall cohort. Compared with men, women were older and had lower prevalence rates of hypertension, coronary artery disease, and chronic kidney disease. Women had diastolic dysfunction more frequently than men (52.8% versus 32.0%, P<0.001). The incidence of the clinical end point did not differ between women and men (women 36.1/100 person-years versus men 30.5/100 person-years, P=0.336). Female sex was independently associated with the echocardiographic end point (adjusted odds ratio, 2.839; 95% CI, 1.884-4.278; P<0.001) and the clinical end point (adjusted hazard ratio, 1.538; 95% CI, 1.143-2.070; P=0.004). Conclusions Female sex was independently associated with the presence of diastolic dysfunction and worse clinical outcomes in a cohort of elderly patients with HFpEF. Our results suggest that a sex-specific approach is key to investigating the pathophysiology of HFpEF. Registration URL: https://upload.umin.ac.jp; Unique identifier: UMIN000021831.
| S-EPMC8174270 | biostudies-literature
Project description:BackgroundThe Wnt signaling pathway, an evolutionarily conserved molecular transduction cascade, has been identified as playing a pivotal role in various physiological and pathological processes of the liver, including homeostasis, regeneration, cirrhosis, and hepatocellular carcinoma (HCC). In this study, we aimed to use a bibliometric method to evaluate the emerging trends on Wnt signaling in liver diseases.MethodsArticles were retrieved from the Web of Science Core Collection. We used a bibliometric software, CiteSpace V 5.3.R4, to analyze the active countries or institutions in the research field, the landmark manuscripts, important subtopics, and evolution of scientific ideas.ResultsIn total, 1,768 manuscripts were published, and each was cited 33.12 times on average. The U.S. published most of the articles, and the most active center was the University of Pittsburgh. The top 5 landmark papers were identified by four bibliometric indexes including citation, burstness, centrality, and usage 2013. The clustering process divided the whole area into nine research subtopics, and the two major important subtopics were "liver zonation" and "HCC." Using the "Part-of-Speech" technique, 1,743 terms representing scientific ideas were identified. After 2008, the bursting phrases were "liver development," "progenitor cells," "hepatic stellate cells," "liver regeneration," "liver fibrosis," "epithelial-mesenchymal transition," and etc.ConclusionUsing bibliometric methods, we quantitatively summarized the advancements and emerging trends in Wnt signaling in liver diseases. These bibliometric findings may pioneer the future direction of this field in the next few years, and further studies are needed.
| S-EPMC6590390 | biostudies-literature
Project description:As part of genetic studies of heart failure in mice, we observed that heart mitochondrial DNA levels and function tend to be reduced in females as compared to males. We also observed that expression of genes encoding mitochondrial proteins were higher in males than females in human cohorts. Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesized that mitochondrial sex differences might underlie this bias. We tested this in a panel of genetically diverse inbred strains of mice, termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, we found that mitochondrial gene expression was highly correlated with diastolic function, a key trait in HFpEF. Consistent with this, studies of a “two-hit” mouse model of HFpEF confirmed that mitochondrial function differed between sexes and was strongly associated with a number of HFpEF traits. By integrating data from human heart failure and the mouse HMDP cohort, we identified the mitochondrial protein Acsl6 as a genetic determinant of diastolic function. We validated its role in HFpEF using adenoviral over-expression in the heart. We conclude that sex differences in mitochondrial function underlie, in part, the sex bias in diastolic function.
2022-01-31 | GSE194151 | GEO