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太空飞行对人类血管平滑肌细胞表型和功能的影响。

Spaceflight effects on human vascular smooth muscle cell phenotype and function.

作者信息

Scotti Marina M, Wilson Brandon K, Bubenik Jodi L, Yu Fahong, Swanson Maurice S, Allen Josephine B

机构信息

Department of Materials Science and Engineering, University of Florida, Gainesville, FL, USA.

Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.

出版信息

NPJ Microgravity. 2024 Mar 28;10(1):41. doi: 10.1038/s41526-024-00380-w.

DOI:10.1038/s41526-024-00380-w
PMID:38548798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10979029/
Abstract

The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths of time in microgravity are subject to cardiovascular deconditioning resulting in loss of vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating the mechanisms by which the cells of the vasculature are altered during spaceflight will be integral to understanding and combating these deleterious effects as the human presence in space advances. In this study, we performed RNA-Seq analysis coupled with review by QIAGEN Ingenuity Pathway Analysis software on human aortic smooth muscle cells (HASMCs) cultured for 3 days in microgravity and aboard the International Space Station to assess the transcriptomic changes that occur during spaceflight. The results of our RNA-Seq analysis show that SMCs undergo a wide range of transcriptional alteration while in space, significantly affecting 4422 genes. SMCs largely down-regulate markers of the contractile, synthetic, and osteogenic phenotypes including smooth muscle alpha actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs). Additionally, components of several cellular signaling pathways were strongly impacted including the STAT3, NFκB, PI3K/AKT, HIF1α, and Endothelin pathways. This study highlights the significant changes in transcriptional behavior SMCs exhibit during spaceflight and puts these changes in context to better understand vascular function in space.

摘要

心血管系统受到太空飞行危害的强烈影响。在微重力环境中停留时间不断增加的宇航员会出现心血管功能失调,导致血管张力丧失、总血容量减少和心输出量降低。随着人类在太空的活动不断推进,了解血管系统细胞在太空飞行期间发生改变的机制对于理解和对抗这些有害影响至关重要。在本研究中,我们对在国际空间站微重力环境下培养3天的人主动脉平滑肌细胞(HASMCs)进行了RNA测序分析,并通过QIAGEN Ingenuity Pathway Analysis软件进行评估,以确定太空飞行期间发生的转录组变化。我们的RNA测序分析结果表明,平滑肌细胞在太空中会发生广泛的转录改变,显著影响4422个基因。平滑肌细胞在很大程度上下调了收缩、合成和成骨表型的标志物,包括平滑肌α肌动蛋白(αSMA)、基质金属蛋白酶(MMPs)和骨形态发生蛋白(BMPs)。此外,几种细胞信号通路的成分也受到强烈影响,包括STAT3、NFκB、PI3K/AKT、HIF1α和内皮素通路。本研究突出了平滑肌细胞在太空飞行期间表现出的转录行为的显著变化,并将这些变化置于相应背景中,以更好地理解太空环境下的血管功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/1e710b71984e/41526_2024_380_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/7a3b72a7afc9/41526_2024_380_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/6331dc582a0d/41526_2024_380_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/ff28133cf7ad/41526_2024_380_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/d4b197698bc9/41526_2024_380_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/1e710b71984e/41526_2024_380_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/7a3b72a7afc9/41526_2024_380_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/6331dc582a0d/41526_2024_380_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/dc2124e95bdf/41526_2024_380_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/ff28133cf7ad/41526_2024_380_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/d4b197698bc9/41526_2024_380_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d95/10979029/1e710b71984e/41526_2024_380_Fig6_HTML.jpg

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