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...

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Autores principales: Ya-Ju Chang, Fatima Tuz-Zahra, Suneeta Godbole, Yesenia Avitia, John Bellettiere, Cheryl L. Rock, Marta M. Jankowska, Matthew A. Allison, David W. Dunstan, Brinda Rana, Loki Natarajan, Dorothy D. Sears
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:1b9918947061439cb6d612fa5bef1c412021-12-02T15:02:49ZEndothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women10.1038/s41598-021-90154-12045-2322https://doaj.org/article/1b9918947061439cb6d612fa5bef1c412021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90154-1https://doaj.org/toc/2045-2322Abstract 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.Ya-Ju ChangFatima Tuz-ZahraSuneeta GodboleYesenia AvitiaJohn BellettiereCheryl L. RockMarta M. JankowskaMatthew A. AllisonDavid W. DunstanBrinda RanaLoki NatarajanDorothy D. SearsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ya-Ju Chang
Fatima Tuz-Zahra
Suneeta Godbole
Yesenia Avitia
John Bellettiere
Cheryl L. Rock
Marta M. Jankowska
Matthew A. Allison
David W. Dunstan
Brinda Rana
Loki Natarajan
Dorothy D. Sears
Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
description 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.
format article
author Ya-Ju Chang
Fatima Tuz-Zahra
Suneeta Godbole
Yesenia Avitia
John Bellettiere
Cheryl L. Rock
Marta M. Jankowska
Matthew A. Allison
David W. Dunstan
Brinda Rana
Loki Natarajan
Dorothy D. Sears
author_facet Ya-Ju Chang
Fatima Tuz-Zahra
Suneeta Godbole
Yesenia Avitia
John Bellettiere
Cheryl L. Rock
Marta M. Jankowska
Matthew A. Allison
David W. Dunstan
Brinda Rana
Loki Natarajan
Dorothy D. Sears
author_sort Ya-Ju Chang
title Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
title_short Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
title_full Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
title_fullStr Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
title_full_unstemmed Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
title_sort endothelial-derived cardiovascular disease-related micrornas elevated with prolonged sitting pattern among postmenopausal women
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1b9918947061439cb6d612fa5bef1c41
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