HDL-microRNA Intercellular Communication in Atherosclerosis

动脉粥样硬化中的 HDL-microRNA 细胞间通讯

• 批准号: 8946167
• 负责人: Kasey C Vickers
• 金额: $ 44.03万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-02 至 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8946167
• 关键词: Animals; Antiatherogenic; Atherosclerosis; Biological; Biological Process; Biology; Blood; Bone Marrow; Bone Marrow Transplantation; Cardiovascular Diseases; Cardiovascular system; Cell Communication; Cells; Chemicals; Cholesterol Homeostasis; Communication; Complex; Data; Disease; Distal; Drug Targeting; Endocrine; Endothelial Cells; Equipment; Extracellular Fluid; Familial Hypercholesterolemia; Functional disorder; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Goals; Health; High Density Lipoproteins; High-Throughput Nucleotide Sequencing; Homeostasis; Hormones; Human; In Vitro; Inflammation; Inflammatory; Knockout Mice; Lesion; Link; Lipoproteins; Maps; Mediating; Metabolic; Metabolism; Methods; MicroRNAs; Modeling; Mus; Nucleic Acids; Organ; Outcome; Pathway interactions; Pharmacotherapy; Phenotype; Physiological; Plasma; Play; Property; Publishing; Regulation; Regulator Genes; Reporting; Role; SR-BI receptor; Societies; Sphingomyelinase; Tissues; Transplantation; Wild Type Mouse; Work; base; circulating microRNA; extracellular; human subject; hypercholesterolemia; in vivo; insight; intercellular communication; locked nucleic acid; macrophage; mimetics; mouse model; new therapeutic target; novel; particle; prevent; public health relevance; reverse cholesterol transport; therapeutic target; uptake

 DESCRIPTION (provided by applicant): Extracellular microRNAs (miRNA) are transported between organs in plasma by protective carriers, including high-density-lipoproteins (HDL). Cardiovascular disease (CVD) represents a significant health and financial burden to our society; however, miRNAs are a new class of drug targets that may be used to treat atherosclerosis. Our published reports and preliminary data suggest that HDL-miRNAs likely serve as biological hormones that regulate systemic homeostasis and have potential to be controlled to treat or prevent CVD. Atherosclerosis is a complex pathophysiology mediated by extensive cell-to-cell communication and gene regulation. The main objectives of this study are to define novel HDL-miRNA intercellular communication mechanisms and the physiological impact of HDL-miRNA communication in CVD. To complete these goals we will, i.) Map the distribution of HDL-miRNA communication and gene regulation, ii.) Identify novel HDL-miRNA target genes associated with inflammation and metabolism, iii.) Determine the role HDL-miR-223 plays in atherosclerosis, and iv.) Control HDL-miRNA communication to treat metabolic dysregulation and atherosclerosis. Collectively, this study will provide remarkable and fundamental insight into HDL biology, and defines the functional relevance and consequences of HDL-miRNA communication in health and disease in animals and humans. As constructed, these studies will take advantage of current concepts in lipoprotein biology and use state-of-the art methods and equipment, including extensive use of high-throughput sequencing.

 描述(申请人提供)：细胞外微小RNA(MiRNA)通过保护性载体在血浆中的器官之间运输，包括高密度脂蛋白(HDL)。心血管疾病(CVD)给我们的社会带来了巨大的健康和经济负担；然而，miRNAs是一类可用于治疗动脉粥样硬化的新型药物靶点。我们已发表的报告和初步数据表明，高密度脂蛋白-miRNAs很可能作为生物激素调节全身的动态平衡，并有可能被控制以治疗或预防心血管疾病。动脉粥样硬化是一种由广泛的细胞间通讯和基因调控介导的复杂的病理生理过程。本研究的主要目的是明确新的高密度脂蛋白-miRNA细胞间通讯机制以及高密度脂蛋白-miRNA通讯在心血管疾病中的生理影响。为了完成这些目标，我们将，即。)绘制高密度脂蛋白-miRNA通讯和基因调控的分布图，II。)确定与炎症和代谢相关的新的高密度脂蛋白-miRNA靶基因，III。)确定高密度脂蛋白-miR-223在动脉粥样硬化中的作用，以及iv。)控制高密度脂蛋白-miRNA通讯以治疗代谢紊乱和动脉粥样硬化。总而言之，这项研究将提供对高密度脂蛋白生物学的非凡和基本的见解，并确定高密度脂蛋白-miRNA通信在动物和人类的健康和疾病中的功能相关性和后果。一旦建成，这些研究将利用脂蛋白生物学中的当前概念，并使用最先进的方法和设备，包括广泛使用高通量测序。