Omics based strategies for precision medicine in hypertension and cardiovascular disease.

基于组学的高血压和心血管疾病精准医疗策略。

• 批准号: 2452382
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2452382
• 关键词: Omics; based; strategies; precision; medicine

Studentship strategic priority area: Basic and Clinical ResearchKeywords:Hypertension, Endocrinology, miRNAs, Precision Medicine, Bioinformatics. High Blood pressure affects up to 50% of the general population and is the major risk factor for cardiovascular disease. Up to 15% of hypertension has an endocrine cause resulting from excessive hormone production and leading to a range of co-morbidities that include stroke, heart failure, atrial fibrillation, left ventricular hypertrophy and obesity. While endocrine hypertension is readily treatable, its accurate diagnosis is time-consuming and costly, which delays the administration of appropriate treatment.Like other forms of hypertension, endocrine hypertension has a genetic component that predisposes individuals to disease. Recent studies identify microRNAs as important regulators of genetic processes. MicroRNAs are small (~22 nucleotide) non-coding RNAs that bind to specific target messenger RNAs, resulting in gene silencing through translation inhibition or mRNA degradation, thereby altering gene expression and protein levels. They have been shown to play a key role in numerous important cellular processes such as oncogenesis and cell proliferation, while our own previous studies also demonstrate a significant effect of microRNAs on hormone secretion, specifically the adrenal corticosteroids that play such a key role in certain forms of endocrine hypertension. Crucially, microRNAs are released by tissues into the bloodstream where they circulate in a stable, cell-free form, with the potential to serve as stable and accessible biomarkers for specific disease states. For this reason, circulating miRNAs represent not only a valuable diagnostic tool but may also be markers of processes that lead to disease and therefore potential therapeutic targets. We hypothesise that circulating miRNA levels are altered in endocrine hypertension and that they can be used as a minimally invasive method to differentiate the various endocrine hypertension subtypes. We are currently part of a large international study (ENSAT-HT) and we have measured circulating miRNAs in a large cohort of carefully-phenotyped human subjects with endocrine hypertension. These extensive circulating miRNA profiles will now be studied in greater detail to investigate their diagnostic potential and their role in the underlying pathophysiological mechanisms of these conditions. This translational project will combine our extensive experience of cardiovascular endocrinology research with cutting-edge molecular, analytical and bioinformatic methods. A better understanding of endocrine hypertension and its associated co-morbidities is central to developing new approaches for managing cardiovascular risk and outcome. Identifying a distinctive circulating miRNA signature that could be exploited for early and efficient diagnosis of affected patients would permit targeted management of patients, bringing significant health and economic benefits. Furthermore, this data could pinpoint novel regulatory mechanisms, thus identifying new types of therapy and better-targeted personalised treatments.

学生奖学金战略优先领域：基础和临床研究关键词：高血压、内分泌学、miRNA、精准医学、生物信息学。高血压影响高达50%的普通人群，是心血管疾病的主要危险因素。高达15%的高血压是由激素分泌过多引起的，并导致一系列并发症，包括中风、心力衰竭、心房纤颤、左心室肥大和肥胖。虽然内分泌高血压是容易治疗的，但其准确诊断是耗时和昂贵的，这延误了适当的治疗管理。像其他形式的高血压一样，内分泌高血压具有遗传成分，使个体容易患病。最近的研究表明microRNA是遗传过程的重要调节因子。MicroRNA是小的（约22个核苷酸）非编码RNA，其结合特定的靶信使RNA，通过翻译抑制或mRNA降解导致基因沉默，从而改变基因表达和蛋白质水平。它们已被证明在许多重要的细胞过程中发挥关键作用，如肿瘤发生和细胞增殖，而我们自己以前的研究也证明了microRNA对激素分泌的显着影响，特别是在某些形式的内分泌高血压中发挥关键作用的肾上腺皮质类固醇。至关重要的是，microRNA由组织释放到血液中，在那里它们以稳定的无细胞形式循环，有可能作为特定疾病状态的稳定和可获得的生物标志物。因此，循环中的miRNAs不仅是一种有价值的诊断工具，而且可能是导致疾病的过程的标志物，因此也是潜在的治疗靶点。我们假设循环miRNA水平在内分泌高血压中发生改变，并且它们可以用作区分各种内分泌高血压亚型的微创方法。我们目前是一项大型国际研究（ENSAT-HT）的一部分，我们已经测量了一个大型队列中仔细分型的内分泌高血压人类受试者的循环miRNA。现在将更详细地研究这些广泛的循环miRNA谱，以研究它们的诊断潜力及其在这些疾病的潜在病理生理机制中的作用。这个转化项目将联合收割机结合我们在心血管内分泌学研究方面的丰富经验和尖端的分子、分析和生物信息学方法。更好地了解内分泌高血压及其相关的合并症是开发新的方法来管理心血管风险和结果的核心。识别一种独特的循环miRNA特征，可用于受影响患者的早期和有效诊断，将允许对患者进行靶向管理，带来显著的健康和经济效益。此外，这些数据可以确定新的调节机制，从而确定新的治疗类型和更有针对性的个性化治疗。