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微重力的干燥浸泡模型调节血小板表型、miRNA 特征和循环血浆蛋白生物标志物谱。

A dry immersion model of microgravity modulates platelet phenotype, miRNA signature, and circulating plasma protein biomarker profile.

机构信息

Technological University Dublin, Dublin 9, Ireland.

Cell & Molecular Physiology Group, School of Health & Human Performance, Faculty of Science and Health, Dublin City University, Glasnevin, Dublin 9, Ireland.

出版信息

Sci Rep. 2021 Nov 9;11(1):21906. doi: 10.1038/s41598-021-01335-x.

DOI:10.1038/s41598-021-01335-x
PMID:34753989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8578674/
Abstract

Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.

摘要

地面微重力研究模式已被提议作为研究心血管疾病等慢性与年龄相关疾病病因的创新方法。干式沉浸(DI)已被有效地用于研究身体不活动(PI)和微重力对多个生理系统的后果。在这里,我们研究了 3 天 DI 对血小板表型的因果关系,并与 miRNA 组学和循环生物标志物表达相关。血小板的 miRNA 图谱反映了表型,表型本身对暴露组敏感且可塑,为了履行血小板在血栓形成和止血中的作用,会发生响应性转变。在任何给定时间都会循环异质血小板亚群,其对激活的敏感性不同。通过使用 DI 模型,我们研究了急性 PI 对 12 名健康男性血小板功能的影响。3 天 DI 导致血小板计数、血小板比容、血小板黏附、聚集显著增加,血小板反应指数(PRI)略有升高。我们发现了 15 种蛋白质生物标志物和 22 种 miRNA 的表达水平在 DI 后发生了改变。微重力/身体不活动的 3 天 DI 模型诱导了一种促血栓形成的血小板表型,具有独特的血小板 miRNA 特征,增加了血小板计数和血小板比容。这与独特的循环蛋白生物标志物特征相关。总之,这些发现强调了血小板作为敏感的适应性哨兵和心血管隔室中表观遗传漂移的功能生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/d2c6568ba88d/41598_2021_1335_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/88ac02b3b053/41598_2021_1335_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/d2c6568ba88d/41598_2021_1335_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/95365da47f68/41598_2021_1335_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/1ae5a5725f3b/41598_2021_1335_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/1e6dfd022e75/41598_2021_1335_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/1dd3dada8131/41598_2021_1335_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/1bc0b8741c80/41598_2021_1335_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/204cfa4d69ca/41598_2021_1335_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/88ac02b3b053/41598_2021_1335_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970c/8578674/d2c6568ba88d/41598_2021_1335_Fig8_HTML.jpg

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