血小板:表观遗传漂移的功能性生物标志物

Laura C. Twomey, R. Wallace, Marco Mangone, BernardDegryse, S. Sheridan, M. Harrison, N. Moyna, Gerardene Meade-Murphy, N. Navasiolava, Marc-AntoineCustaud, Ronan P. Murphy
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引用次数: 2

摘要

心血管疾病(CVD)的危险因素可分为可改变的和不可改变的。缺乏运动和肥胖是心血管疾病发生、发展和进展的主要行为危险因素。血小板功能障碍是CVD病因学的关键,CVD是一种慢性血管炎症,其特点是发病和临床表现之间存在滞后时间。这表明表观遗传漂变的作用,由基因表达的随机模式定义,不依赖于编码DNA的动态变化。表观基因组是DNA和组蛋白上的化学标记的集合,在胚胎发生期间形成,并随着年龄和生活方式而改变。非编码RNA(如microRNA)的生物发生和效应功能对基因表达起调控作用,从而调控表观遗传机制。在本章中,我们将通过巨核细胞生成和血小板生成的表观遗传变化,重点关注体力活动/不活动和超重/肥胖等可改变的危险因素对血小板功能的影响。我们还将讨论急性运动对血小板功能的作用以及心肺适能(CRF)对急性运动血小板反应的影响。本章将强调血小板作为表观遗传漂移的循环功能生物标志物的潜在作用,以实施、优化和监测心血管疾病预防管理策略。
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Platelets: Functional Biomarkers of Epigenetic Drift
Cardiovascular disease (CVD) risk factors can be classed as modifiable or non-modifiable. Physical inactivity and obesity represent major behavioural risk factors for the initiation, development and progression of CVD. Platelet dysfunction is pivotal to the aetiology of CVD, a chronic vascular inflammatory condition, which is characterised by a lag time between onset and clinical manifestation. This indicates the role of epigenetic drift, defined by stochastic patterns of gene expression not dependent on dynamic changes in coding DNA. The epigenome, a collection of chemical marks on DNA and histones, is established during embryogenesis and modified by age and lifestyle. Biogenesis and effector function of non-coding RNA, such as microRNA, play a regulatory role in gene expression and thus the epigenetic mechanism. In this chapter, we will focus on the effect of the modifiable risk factors of physical activity/inactivity and overweight/obesity on platelet function, via epigenetic changes in both megakaryocytopoiesis and thrombopoiesis. We will also discuss the role of acute exercise on platelet function and the impact of cardiorespiratory fitness (CRF) on platelet responses to acute exercise. This chapter will highlight the potential role of platelets as circulating functional biomarkers of epigenetic drift to implement, optimise and monitor CVD preventive management strategies.
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