Elsangeedy Ebrahim, Yamaleyeva Dina N, Edenhoffer Nicholas P, Deak Allyson, Soloshenko Anna, Ray Jonathan, Sun Xuming, Shaltout Omar H, Cruz-Diaz Nildris, Westwood Brian, Kim-Shapiro Daniel, Diz Debra I, Soker Shay, Pulgar Victor M, Ronca April, Willey Jeffrey S, Yamaleyeva Liliya M
Department of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
NPJ Microgravity. 2024 Dec 19;10(1):110. doi: 10.1038/s41526-024-00450-z.
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.
男性和女性对太空飞行有不同的心血管反应；然而，很少有研究关注性别之间的直接比较。我们研究了20周龄、社会和性成熟的雄性和雌性Sprague Dawley（SD）大鼠在经历14天的后肢卸载（HLU）后主动脉硬化的机制。与对照雌性大鼠（n = 6 - 8）相比，HLU后雌性大鼠主动脉弓的脉搏波速度（PWV）更高。HLU对雄性大鼠的主动脉PWV没有影响（n = 5 - 6）。HLU后，两性大鼠的主动脉α平滑肌肌动蛋白、肌球蛋白、胶原蛋白、弹性蛋白以及胶原蛋白与弹性蛋白的比值没有差异。与雌性对照相比，暴露于HLU的SD雌性大鼠主动脉中G蛋白偶联雌激素受体（GPER）的水平较低，但在雄性大鼠中没有改变。与对照雌性大鼠相比，HLU雌性大鼠的主动脉PPARγ水平也较低，氧化应激标志物增加，并且存在舒张功能障碍。GPER激动剂G1可防止HLU雌性大鼠（每组n = 4）的PWV和8 - 羟基 - 2'-脱氧鸟苷增加，而不改变PPARγ或p47phox，这表明较低的GPER可能在模拟微重力环境下导致动脉僵硬。这项研究突出了性别特异性的血管对模拟微重力状态的适应性。
