Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease

细胞外 RNA：心血管风险和疾病的生物标志物

基本信息

批准号：
8581770
负责人：
JANE E Freedman
金额：
$ 50万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8581770
关键词：
Acute Adult Atherosclerosis Bedside Testings Biological Assay Biological Markers Blood Circulation Cardiac Cardiovascular Diseases Cells Clinical Clinical Data Cohort Studies Communication Communities Coronary Data Databases Deposition Development Diabetes Mellitus Diagnostic Disease Disease Progression Dyslipidemias Education Endosomes Enrollment Epidemiology Event Exposure to Fireflies Fractionation Framingham Heart Study Genetic Transcription Health Human Hydrogels Hypertension Individual Industry Laboratories Lipids Measurement Measures Messenger RNA Methods MicroRNAs Minority Morbidity - disease rate North America Obesity Outcomes Research Participant Pathogenesis Patients Performance Phase Phenotype Plasma Population Process Proteins Qualifying RNA RNA Sequences Research Research Personnel Resources Risk Factors Risk Marker Robotics Sampling Smoking Stroke Syndrome Techniques Time Untranslated RNA Visit Work acute coronary syndrome base cardiovascular disorder risk cigarette smoking cohort disease phenotype disorder risk experience extracellular fasting glucose follow-up member mortality multidisciplinary new technology offspring outcome forecast particle patient population piRNA pre-clinical prognostic protein expression public health relevance screening

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) and stroke are two of the leading causes of morbidity and mortality among adults in North America and are strongly determined by levels of common CVD risk factors including hypertension, diabetes, obesity, cigarette smoking, and dyslipidemia. Specific extracellular RNAs regulate key processes central to the pathogenesis of CVD and several small human studies have associated extracellular RNAs with specific forms of CVD. We postulate that the expression of plasma RNAs change over time and is influenced by the duration and intensity of exposure to CVD risk factors, relates to subclinical atherosclerosis phenotypes, and will therefore be useful predictors of incident CVD events. We intend to further explore and validate the diagnostic and prognostic utility of extracellular RNAs associated with CVD and preclinical CVD phenotypes in our community-based cohort study in a hospitalized sample with acute coronary syndromes. To accomplish these aims, in the U2 phase of our study we will use an optimized non-commercial isolation method for high-yield plasma RNA extraction as well as high-throughput sequencing to identify known and as-yet undiscovered extracellular circulating RNAs, thereby developing a broad panel of plasma-derived extracellular RNA biomarkers (including miRNA, piRNA, noncoding RNAs) to screen 2914 participants in the Framingham Heart Study (FHS) Study (Offspring Exam 8). In the U3 phase of the application, we will further evaluate changes in circulating RNAs over time and in relation to incident CVD and disease progression, by screening the same individuals 5 years later (Offspring Exam 9). We will then examine associations between extracellular RNAs and CVD-related prognosis in ~400 participants of TRACE-CORE (Transitions and Research in Acute Coronary Events - Center for Outcomes Research and Education). We will perform exploratory analyses to determine if these methods can be extended to non-CVD populations. Last, we will partner with industry leaders to develop a quick and effective point-of-care test for extracellular RNA profiles associated with disease.

描述（由申请人提供）：心血管疾病 (CVD) 和中风是北美成年人发病和死亡的两个主要原因，很大程度上取决于常见 CVD 危险因素的水平，包括高血压、糖尿病、肥胖、吸烟和血脂异常。特定的细胞外 RNA 调节 CVD 发病机制的关键过程，一些小型人类研究已将细胞外 RNA 与特定形式的 CVD 联系起来。我们假设血浆 RNA 的表达随时间变化，并受到 CVD 危险因素暴露时间和强度的影响，与亚临床动脉粥样硬化表型相关，因此将成为 CVD 事件的有用预测因子。我们打算在基于社区的队列研究中，以急性冠脉综合征住院样本为对象，进一步探索和验证与 CVD 和临床前 CVD 表型相关的细胞外 RNA 的诊断和预后效用。为了实现这些目标，在我们研究的 U2 阶段，我们将使用优化的非商业分离方法进行高产血浆 RNA 提取以及高通量测序来识别已知和尚未发现的细胞外循环 RNA，从而开发一系列血浆来源的细胞外 RNA 生物标志物（包括 miRNA、piRNA、非编码 RNA），用于筛选弗雷明汉心脏研究 (FHS) 研究（后代检查）的 2914 名参与者8).在应用的 U3 阶段，我们将通过 5 年后筛查相同的个体（后代检查 9），进一步评估循环 RNA 随着时间的变化以及与 CVD 事件和疾病进展的关系。然后，我们将在 TRACE-CORE（急性冠状动脉事件的转变和研究 - 结果研究和教育中心）的约 400 名参与者中检查细胞外 RNA 与 CVD 相关预后之间的关联。我们将进行探索性分析，以确定这些方法是否可以扩展到非 CVD 人群。最后，我们将与行业领导者合作，开发一种快速有效的细胞外 RNA 即时检测方法与疾病有关。