Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats

Abstract Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffening in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hi...

Full description

Saved in:
Bibliographic Details
Main Authors: Ebrahim Elsangeedy, Dina N. Yamaleyeva, Nicholas P. Edenhoffer, Allyson Deak, Anna Soloshenko, Jonathan Ray, Xuming Sun, Omar H. Shaltout, Nildris Cruz-Diaz, Brian Westwood, Daniel Kim-Shapiro, Debra I. Diz, Shay Soker, Victor M. Pulgar, April Ronca, Jeffrey S. Willey, Liliya M. Yamaleyeva
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:npj Microgravity
Online Access:https://doi.org/10.1038/s41526-024-00450-z
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850253860470259712
author Ebrahim Elsangeedy
Dina N. Yamaleyeva
Nicholas P. Edenhoffer
Allyson Deak
Anna Soloshenko
Jonathan Ray
Xuming Sun
Omar H. Shaltout
Nildris Cruz-Diaz
Brian Westwood
Daniel Kim-Shapiro
Debra I. Diz
Shay Soker
Victor M. Pulgar
April Ronca
Jeffrey S. Willey
Liliya M. Yamaleyeva
author_facet Ebrahim Elsangeedy
Dina N. Yamaleyeva
Nicholas P. Edenhoffer
Allyson Deak
Anna Soloshenko
Jonathan Ray
Xuming Sun
Omar H. Shaltout
Nildris Cruz-Diaz
Brian Westwood
Daniel Kim-Shapiro
Debra I. Diz
Shay Soker
Victor M. Pulgar
April Ronca
Jeffrey S. Willey
Liliya M. Yamaleyeva
author_sort Ebrahim Elsangeedy
collection DOAJ
description Abstract Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffening in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) for 14 days. Pulse wave velocity (PWV) was greater in the aortic arch of females after HLU versus control females (n = 6–8). HLU had no effect on aortic PWV in males (n = 5–6). Aortic α smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex following HLU. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but were not altered in males. HLU females also had lower aortic PPARγ, increased oxidative stress markers, and diastolic dysfunction compared with control females. GPER agonist G1 prevented the increase in PWV and 8-hydroxy-2’-deoxyguanosine without altering PPARγ or p47phox in HLU females (n = 4 in each group) suggesting that lower GPER may contribute to arterial stiffening in the setting of simulated microgravity. This study highlights sex-specific vascular adaptations to the state of simulated microgravity.
format Article
id doaj-art-11bf1bf4b70844e6a8de2fa51ae895d4
institution OA Journals
issn 2373-8065
language English
publishDate 2024-12-01
publisher Nature Portfolio
record_format Article
series npj Microgravity
spelling doaj-art-11bf1bf4b70844e6a8de2fa51ae895d42025-08-20T01:57:16ZengNature Portfolionpj Microgravity2373-80652024-12-0110111610.1038/s41526-024-00450-zSex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley ratsEbrahim Elsangeedy0Dina N. Yamaleyeva1Nicholas P. Edenhoffer2Allyson Deak3Anna Soloshenko4Jonathan Ray5Xuming Sun6Omar H. Shaltout7Nildris Cruz-Diaz8Brian Westwood9Daniel Kim-Shapiro10Debra I. Diz11Shay Soker12Victor M. Pulgar13April Ronca14Jeffrey S. Willey15Liliya M. Yamaleyeva16Department of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineWake Forest Institute for Regenerative Medicine, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineDepartment of Physics, Wake Forest UniversityDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineWake Forest Institute for Regenerative Medicine, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineNASA Ames Research Center, Space Biosciences DivisionDepartment of Radiation Oncology, Wake Forest University School of MedicineDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of MedicineAbstract Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffening in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) for 14 days. Pulse wave velocity (PWV) was greater in the aortic arch of females after HLU versus control females (n = 6–8). HLU had no effect on aortic PWV in males (n = 5–6). Aortic α smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex following HLU. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but were not altered in males. HLU females also had lower aortic PPARγ, increased oxidative stress markers, and diastolic dysfunction compared with control females. GPER agonist G1 prevented the increase in PWV and 8-hydroxy-2’-deoxyguanosine without altering PPARγ or p47phox in HLU females (n = 4 in each group) suggesting that lower GPER may contribute to arterial stiffening in the setting of simulated microgravity. This study highlights sex-specific vascular adaptations to the state of simulated microgravity.https://doi.org/10.1038/s41526-024-00450-z
spellingShingle Ebrahim Elsangeedy
Dina N. Yamaleyeva
Nicholas P. Edenhoffer
Allyson Deak
Anna Soloshenko
Jonathan Ray
Xuming Sun
Omar H. Shaltout
Nildris Cruz-Diaz
Brian Westwood
Daniel Kim-Shapiro
Debra I. Diz
Shay Soker
Victor M. Pulgar
April Ronca
Jeffrey S. Willey
Liliya M. Yamaleyeva
Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats
npj Microgravity
title Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats
title_full Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats
title_fullStr Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats
title_full_unstemmed Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats
title_short Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats
title_sort sex specific cardiovascular adaptations to simulated microgravity in sprague dawley rats
url https://doi.org/10.1038/s41526-024-00450-z
work_keys_str_mv AT ebrahimelsangeedy sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT dinanyamaleyeva sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT nicholaspedenhoffer sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT allysondeak sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT annasoloshenko sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT jonathanray sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT xumingsun sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT omarhshaltout sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT nildriscruzdiaz sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT brianwestwood sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT danielkimshapiro sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT debraidiz sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT shaysoker sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT victormpulgar sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT aprilronca sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT jeffreyswilley sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats
AT liliyamyamaleyeva sexspecificcardiovascularadaptationstosimulatedmicrogravityinspraguedawleyrats