与心血管疾病相关的航天飞行和飞行后基因表达的可塑性:机制和候选再用途药物。

IF 3.9 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Proteomics Pub Date : 2025-04-14 DOI:10.1002/pmic.202400241
Marilena M. Bourdakou, Eleni M. Loizidou, George M. Spyrou
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引用次数: 0

摘要

由于暴露于宇宙辐射、微重力和相关氧化应激水平的增加,航天飞行对人类健康构成了独特的挑战。这些环境因素可导致细胞损伤、炎症和一系列健康并发症,包括心血管问题、免疫系统损伤和癌症风险增加。核因子红系2相关因子2 (Nuclear factor erythroid 2-related factor 2, NRF2)是一种通过促进抗氧化酶的表达来调节机体抗氧化应激防御机制的关键转录因子。最近的研究进一步阐明了NRF2在解决与空间有关的健康挑战方面的关键作用。在这项研究中,我们开发了一种计算方法来探索飞行和飞行后条件下基因表达谱的可塑性,突出显示了不返回地面水平并与心血管疾病(CVD)相关的基因特征相关的基因及其相应机制。来自人诱导多能干细胞衍生心肌细胞(hiPSC-CMs)的RNA测序(RNA-seq)数据已被用于研究微重力对心功能的细胞影响。进行基因表达单调性研究,并将其与全基因组关联研究(GWAS)联系起来,以突出与心血管疾病相关的单调表达基因。选择的单调表达基因也被映射到NRF2网络上,以研究在氧化还原信号通路的背景下,太空飞行对人类心肌细胞功能的影响。基于这些知识,我们使用计算药物再利用方法提出了一份简短的候选药物再利用清单,这些候选药物可以在宇航员中进一步测试,以预防心血管疾病。该研究为太空飞行诱导心肌细胞的分子和氧化还原信号改变提供了见解,为未来旨在减轻宇航员心血管风险和推进地球临床应用的研究奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs

Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs

Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs

Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs

Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs

Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs

Spaceflight poses unique challenges to human health due to exposure to increased levels of cosmic radiation, microgravity, and associated oxidative stress. These environmental factors can lead to cellular damage, inflammation, and a range of health complications, including cardiovascular problems, immune system impairment, and an increased risk of cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the body's defense mechanisms against oxidative stress by promoting the expression of antioxidant enzymes. Recent research has shed more light on the critical role of NRF2 in addressing space-related health challenges. In this study, we developed a computational methodology to explore the plasticity of the gene expression profile in flight and postflight conditions, highlighting the genes and corresponding mechanisms that do not return to ground levels and correlate with gene signatures associated with cardiovascular disease (CVD). RNA sequencing (RNA-seq) data from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used to investigate the cellular effects of microgravity on cardiac function. Gene expression monotonicity studies were performed and linked to genome-wide association studies (GWAS) to highlight the monotonically expressed genes associated with CVD. The selected monotonically expressed genes were also mapped onto the NRF2 network to investigate the impact of spaceflight on human cardiomyocyte function in the context of redox signaling pathways. Based on this knowledge, we used computational drug repurposing methods to suggest a short list of repurposed drug candidates that can be further tested in astronauts for the prevention of CVD. This study provides insights into the molecular and redox signaling alterations in cardiomyocytes induced by spaceflight, laying the foundation for future research aimed at mitigating cardiovascular risks in astronauts and advancing clinical applications on Earth.

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来源期刊
Proteomics
Proteomics 生物-生化研究方法
CiteScore
6.30
自引率
5.90%
发文量
193
审稿时长
3 months
期刊介绍: PROTEOMICS is the premier international source for information on all aspects of applications and technologies, including software, in proteomics and other "omics". The journal includes but is not limited to proteomics, genomics, transcriptomics, metabolomics and lipidomics, and systems biology approaches. Papers describing novel applications of proteomics and integration of multi-omics data and approaches are especially welcome.
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