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：
9325089
负责人：
JANE E Freedman
金额：
$ 93.74万
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 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9325089
关键词：
Acute Coronary Event Adult Atherosclerosis Bedside Testings Biological Assay Biological Markers Blood Circulation Cardiac Cardiovascular Diseases Cells Clinical Clinical Data Cohort Studies Communication Communities 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 High-Throughput Nucleotide Sequencing High-Throughput RNA Sequencing 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 Quantitative Reverse Transcriptase PCR RNA RNA Sequences Research Research Personnel Risk Factors Risk Marker Robotics Sampling Smoking Stroke Syndrome Techniques Thromboplastin Time Untranslated RNA Visit acute coronary syndrome base cardiovascular disorder risk cardiovascular risk factor cigarette smoking cohort data resource diagnostic biomarker disease phenotype disorder risk experience extracellular fasting glucose follow-up member mortality multidisciplinary new technology offspring outcome forecast particle patient population piRNA pre-clinical prehypertension prognostic protein expression public health relevance screening transcriptome sequencing

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）和中风是北美成人发病率和死亡率的两个主要原因，并由普通CVD危险因素的水平强烈决定，包括高血压，糖尿病，肥胖，吸烟和血脂症。特定的细胞外RNA调节CVD发病机理的关键过程，而几项小型人类研究将细胞外RNA与特定形式的CVD相关联。我们假设血浆RNA的表达会随着时间的流逝而变化，并且受到CVD风险因素的持续时间和强度的影响，与亚临床动脉粥样硬化表型有关，因此将是事件CVD事件的有用预测指标。我们打算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，在我们的基于社区的同类研究中，在患有急性冠状动脉综合征的住院样本中。为了实现这些目的，在我们研究的U2阶段，我们将使用一种优化的非商业隔离方法进行高产等离子体RNA提取以及高通量测序，以识别已知且尚未发现的未发现的细胞外循环RNA，从而开发出宽面积的杂质细胞界面RNA生物NONNA，包括RNA的宽面层（包括），包括RNA，包括miRNA，包括pirna，包括pirna，包括pirnna serc）， 2914名Framingham心脏研究（FHS）研究（后代考试8）的参与者。在应用程序的U3阶段，我们将通过5年后筛选相同的个体（后代考试9），进一步评估循环RNA的变化以及与事件CVD和疾病进展有关的变化。然后，我们将研究约有400名微量核参与者（急性冠状动脉事件的过渡和研究 - 结果研究与教育中心）的细胞外RNA和与CVD相关的预后之间的关联。我们将执行探索性分析，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，为细胞外RNA概况开发快速有效的护理测试与疾病有关。