Endothelial‐Derived MicroRNAs are Novel Biomarkers Reflecting Prolonged Sitting Pattern and Physical Activity in Postmenopausal Women: Possible Ethnic Differences

Abstract

Background and HypothesisDuring waking hours, older adults spend the most time sitting and are least likely to meet physical activity guidelines. Such a sedentary lifestyle is associated with cardiovascular and coronary heart disease mortality risk, particularly in postmenopausal Hispanic/Latino women. The deleterious impact of prolonged sitting includes endothelial dysfunction, which favors atherosclerotic initiation. Extracellular vesicles (EVs) are potential biomarkers of physiologic function, which carry molecular cargo from the parent cell, including metabolites, proteins, and nucleic acids, that reflect the cell’s biological health status. Some EV cargo, such as microRNAs (miRs), are capable of mediating cell‐to‐cell communication. We hypothesize that miRs encapsulated in endothelial cell (EC)‐derived EVs serve as molecular transducers bridging prolonged sitting with cardiovascular disease (CVD) risk.ObjectiveIdentify potential miR transducers associated with prolonged sitting durations.Materials, Methods, and ResultsArchival behavior data and plasma samples were used from a population of 518 women participants, aged ≥55 years and BMI ≥25kg/m2, from the UCSD Metabolic, Exercise, and Nutrition, Reach for Health, and Community of Mine studies. Objective measures of sitting posture and moderate‐to‐vigorous physical activity (MVPA) were collected from participants using waist‐worn ActiGraph. We identified subpopulations of women who had low MVPA and the shortest or longest mean sitting bout duration across quartiles as Interrupted Sitters (IS, n=18) or Super Sitters (SS, n=53), respectively. CD144+EVs representing EC‐EVs were immunoprecipitated from archival plasma samples for miR profiling. Five target miRs (miR‐199a‐5p, let‐7d‐5p, miR‐140‐5p, miR‐142‐3p, miR‐133b) potentially associated with sitting patterns were identified using Qiagen miScript miR PCR Array Human Cardiovascular disease, employing propensity score balance for confounding factors. Technical validation by qPCR corroborated that 3 miRs had significantly greater expressions in EC‐EVs from SS, compared to IS. The significance of this expression difference was sustained in the non‐Hispanic subpopulation, but only miR‐133b was still significantly different between the two groups in the Hispanic subpopulation. Moreover, miR‐133b expression, but not miR‐199a‐5p, let‐7d‐5p, or miR‐140‐5p expression, in the SS Hispanic group decreased with increased MVPA.ConclusionEC‐EVs carrying CVD‐related miRs may be promising for monitoring prolonged sitting patterns in overweight postmenopausal women, which may differ by ethnicity.Support or Funding InformationAmerican Heart Association Go Red For Women Strategically Focused Network grant (16SFRN28420000) and the National Institutes of Health: Community of Mine (R01 CA179977), Reach for Health (U54 CA155435) and Metabolism, Exercise and Nutrition at UCSD (MENU; U54 CA155435 and also the California Walnut Commission), and training grant from NHLBI (T32 HL079891).