Molecular and Cellular Characterization of Space Flight Effects on Microvascular Endothelial Cell Function - PreparatoryWork for the SFEF Project

Molecular and Cellular Characterization of Space Flight Effects on Microvascular Endothelial Cell Function - PreparatoryWork for the SFEF Project
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DOI:
10.1007/s12217-014-9399-4
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发表时间:
2014-12-01
影响因子:
1.8
通讯作者:
Angeloni, Debora
Angeloni, Debora
中科院分区:
工程技术4区
文献类型:
--
作者:
Balsamo, Michele;Barravecchia, Ivana;Angeloni, Debora

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在不同长度的空间飞行期间暴露于微重力会引起内皮细胞(所有血管的细胞)的痛苦,这是宇航员和从太空返回的动物发现的健康问题的主要原因。前疾病学医学感兴趣的是,微重力对宇航员的影响与地球上久坐不动的生活,衰老和退行性疾病的后果惊人地相似,尽管SF效应是加速和可逆的。因此,微重力是更好地了解常见病理学的一个重要的新模型。一个全面的细胞和分子生物学研究是必要的,以解释SF后的病理生理学结果。该项目将通过分析1)细胞转录组,2)DNA甲基化组,3)DNA损伤和细胞衰老,4)细胞周期和细胞形态的变化,研究微重力和宇宙辐射对在国际空间站上培养的内皮细胞的影响。该项目已被欧洲航天局和意大利航天局选定,目前正在筹备之中。这里提出的地面研究是为了确定生物和工程要求,使我们能够在太空中培养,固定和储存EC后检索合适的样品。我们希望确定微血管内皮细胞中由空间微重力激活的分子通路,这可能有助于揭示导致宇航员和地球上受衰老,退行性和久坐生活相关病理影响的个体共同遭受内皮痛苦的致病分子机制。
Exposure to microgravity during space flight (SF) of variable length induces suffering of the endothelium (the cells lining all blood vessels), mostly responsible for health problems found in astronauts and animals returning from space. Of interest to pre-nosological medicine, the effects of microgravity on astronauts are strikingly similar to the consequences of sedentary life, senescence and degenerative diseases on Earth, although SF effects are accelerated and reversible. Thus, microgravity is a significant novel model for better understanding of common pathologies. A comprehensive cell and molecular biology study is needed in order to explain pathophysiological findings after SFs. This project will study the effects of microgravity and cosmic radiation on endothelial cells (ECs) cultured on the International Space Station through analysis of 1) cell transcriptome, 2) DNA methylome, 3) DNA damage and cell senescence, 4) variations in cell cycle and cell morphology. This project has been selected by the European Space Agency and the Italian Space Agency and is presently in preparation. The ground study presented here was performed to determine the biological and engineering requirements that will allow us to retrieve suitable samples after culturing, fixing and storing ECs in space. We expect to identify molecular pathways activated by space microgravity in microvascular ECs, which may shed light on pathogenic molecular mechanisms responsible for endothelial suffering shared by astronauts and individuals affected with aging, degenerative and sedentary life-associated pathologies on Earth.