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Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women.

ABSTRACT: Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated from endothelial cell (EC)-derived EVs. Using extant actigraphy based sitting behavior data on a cohort of 518 postmenopausal overweight/obese women, we grouped the woman as Interrupted Sitters (IS; N = 18) or Super Sitters (SS; N = 53) if they were in the shortest or longest sitting pattern quartile, respectively. The cargo microRNA in EC-EVs from the IS and SS women were compared. MicroRNA data were weighted by age, physical functioning, MVPA, device wear days, device wear time, waist circumference, and body mass index. Screening of CVD-related microRNAs demonstrated that miR-199a-5p, let-7d-5p, miR-140-5p, miR-142-3p, miR-133b level were significantly elevated in SS compared to IS groups. Group differences in let-7d-5p, miR-133b, and miR-142-3p were validated in expanded groups. Pathway enrichment analyses show that mucin-type O-glycan biosynthesis and cardiomyocyte adrenergic signaling (P < 0.001) are downstream of the three validated microRNAs. This proof-of-concept study supports the possibility that CVD-related microRNAs in EC-EVs may be molecular transducers of sitting pattern-associated CVD risk in overweight postmenopausal women.

SUBMITTER: Chang YJ

PROVIDER: S-EPMC8175392 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women.

Chang Ya-Ju YJ Tuz-Zahra Fatima F Godbole Suneeta S Avitia Yesenia Y Bellettiere John J Rock Cheryl L CL Jankowska Marta M MM Allison Matthew A MA Dunstan David W DW Rana Brinda B Natarajan Loki L Sears Dorothy D DD

Scientific reports 20210603 1

Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated from endothelial cell (EC)-derived EVs. Using extant actigraphy based sitting behavior data on a cohort of 518 postmenopausal overweight/obese women, ...[more]

PMID: 34083573

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Project description:Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted.

Project description:BackgroundThe preferred macronutrient dietary composition, and the health consequences of dietary fat reduction specifically, have been debated for decades. Here we provide a comprehensive overview of long-term health outcomes in the Women's Health Initiative Dietary Modification (DM) trial.ObjectiveThe DM trial aimed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer, colorectal cancer, and, secondarily, coronary heart disease (CHD), with various other health outcomes also considered.MethodsThe DM trial is a randomized controlled trial conducted at 40 centers in the US, among 48,835 postmenopausal women aged 50-79 y with baseline intake of ≥32% energy from fat. Participants were randomly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group, during 1993-1998. Intervention goals were to reduce fat intake from ∼35% to 20% of total energy, in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d.ResultsOver an 8.5-y (median) intervention period, intervention and comparison group differences included lower fat by 8-10%, and higher carbohydrate by 8-10%, of total energy, in conjunction with higher consumption of vegetables, fruit, and grains. Time-to-outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer, colorectal cancer, or CHD, either over the intervention period or over longer-term cumulative follow-up. Additional analyses showed significant intervention group benefits related to breast cancer, CHD, and diabetes, without adverse effects. Over a 19.6-y (median) follow-up period, HRs (95% CIs) were 0.84 (0.74, 0.96) for breast cancer followed by death, and 0.87 (0.77, 0.98) for diabetes requiring insulin.ConclusionsReduction in dietary fat with corresponding increase in vegetables, fruit, and grains led to benefits related to breast cancer, CHD, and diabetes, without adverse effects, among healthy postmenopausal US women.This trial was registered at clinicaltrials.gov as NCT00000611.

Project description:BackgroundMany older adults spend the majority of their waking hours sitting, which increases their risk of chronic diseases. Given the challenges that many older adults face when engaging in moderate-to-vigorous physical activity, understanding the health benefits of decreasing sitting time and increasing the number of sit-to-stand transitions is needed to address this growing public health concern.ObjectiveThe aim of this 3-arm randomized controlled trial is to investigate how changes in sitting time and brief sit-to-stand transitions impact biomarkers of healthy aging and physical, emotional, and cognitive functioning compared with a healthy attention control arm.MethodsSedentary and postmenopausal women (N=405) will be recruited and randomly assigned to 1 of the 3 study conditions for 3 months: healthy living attention control (Healthy Living), reduce sitting time (Reduce Sitting), and increase sit-to-stand transitions (Increase Transitions). Assessments conducted at baseline and 3 months included fasting blood draw, blood pressure, anthropometric measurements, physical functioning, cognitive testing, and 7 days of a thigh-worn accelerometer (activPAL) and a hip-worn accelerometer (ActiGraph). Blood-based biomarkers of healthy aging included those associated with glycemic control (glycated hemoglobin, fasting plasma insulin and glucose, and homeostatic model assessment of insulin resistance).ResultsRecruitment began in May 2018. The intervention is ongoing, with data collection expected to continue through the end of 2022.ConclusionsThe Rise for Health study is designed to test whether 2 different approaches to interrupting sitting time can improve healthy aging in postmenopausal women. Results from this study may inform the development of sedentary behavior guidelines and interventions to reduce sitting time in older adults.Trial registrationClinicalTrials.gov NCT03473145; https://clinicaltrials.gov/ct2/show/NCT03473145.International registered report identifier (irrid)DERR1-10.2196/28684.

Project description:BackgroundProlonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear.MethodsIn preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size.ResultsNine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p = 0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10-minute standing every hour condition resulted in an improved FMD response, which was significantly greater than the control condition after Bonferroni correction (p = 0.0033).ConclusionThis study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population. Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed.Trial registrationClinicalTrials.gov NCT02743286.

Project description:BackgroundProlonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels.MethodsAmong 1804 postmenopausal women enrolled in the Women's Health Initiative Observational Study, 15 serum oestrogens/oestrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting were self-reported via questionnaire. Using baseline, cross-sectional data, geometric means (GM) of oestrogens/oestrogen metabolites (pmol l-1) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use.ResultsLonger time spent sitting (⩾10 vs ⩽5h per day) was associated with higher levels of unconjugated oestrone, independent of moderate- to vigorous-intensity physical activity and body mass index, among both never/former (GM=70.6 vs 57.7) and current MHT users (GM=242 vs 179) (P-trend ⩽0.03). Among never/former MHT users, sitting (⩾10 vs ⩽5h per day) was positively associated with 2-methoxyestradiol (GM=16.4 vs 14.4) and 4-methoxyestradiol (GM=2.36 vs 1.98) (P-trend ⩽0.04), independent of parent oestrogens. Inverse associations between moderate- to vigorous-intensity physical activity (⩾15 vs 0 metabolic equivalent task-hours per week) and parent oestrogens were found as expected. After adjustment for parent oestrogens, physical activity was not associated with oestrogen metabolites.ConclusionsOur data suggest that prolonged sitting and lower moderate- to vigorous-intensity physical activity are associated with higher levels of postmenopausal oestrogens/oestrogen metabolites, the oestrogen metabolism patterns that have previously been associated with higher endometrial and breast cancer risk.

Dataset Information

Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women.

Publications

Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women.

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