Molecular networks of epicardial formation and function

心外膜形成和功能的分子网络

基本信息

批准号：
9384315
负责人：
Frank Leo Conlon
金额：
$ 53.23万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9384315
关键词：
Address Adult Affect American Animal Model Biochemical Biological Assay Biology Bone Morphogenetic Proteins C-Terminal Binding Protein 2 Cardiac Cardiac development Cause of Death Cell Maturation Cells Complex Congenital Abnormality Data Defect Development Disease Down-Regulation Embryo Endocardium Epicardium Event Failure Fibroblasts Foundations Genetic Genetic Transcription Heart Heart Valves Hemostatic function Human Infant Mortality Invaded Ligands Maps Mediating Mediator of activation protein Molecular Myocardial Myocardium Neonatal Nuclear Organ Organ Transplantation Pathway interactions Phenotype Physiological Protein Inhibition Proteins Proteomics Reagent Role Series Signal Pathway Signal Transduction Signaling Protein Smooth Muscle Myocytes Structural Congenital Anomalies Structure Structure of septum transversum Surface System Technology Testing Time Tissues Transforming Growth Factor beta Transgenic Organisms Tube Vertebrates Western World Xenopus base cardiogenesis cell type chordin congenital heart disorder gene repression in vivo inhibitor/antagonist insight migration mutant novel protein complex protein expression protein function repaired transcription factor

项目摘要

ABSTRACT Congenital heart disease is the leading cause of death in the western world affecting approximately 1.3 million Americans. The heart initially forms in vertebrates as a bilaminar tube comprised of an inner endocardium and outer myocardial layer. At later stages of development a third layer is added to the heart from the epicardium which forms from a dynamic precursor structure, the proepicardial organ (PEO) which forms on the septum transversum, a structure adjacent to the heart. As the embryo matures, cells from the PEO migrate onto the heart surface ultimately giving rise to several essential cell types in the adult heart including cardiac fibroblasts and the smooth muscle cells of the vasculature. The aim of this proposal will leverage our series of unique technologies, reagents, and animal models to elucidate the molecular and cellular pathways required for the formation and function of the epicardium. In doing so, we will provide a platform for studying heart formation and hemostasis, and thus proved mechanistic insight into human congenital heart disease.

抽象的先天性心脏病是西方世界中死亡的主要原因，影响约1.3 百万美国人。心脏最初是在脊椎动物中形成的，作为双肌管，由内部组成心内膜和外心肌层。在开发的后期阶段，第三层被添加到心外膜的心脏由动态前体结构形成，头皮器官（PEO）在隔膜横向上形成，该结构与心脏相邻。作为胚胎成熟，PEO的细胞迁移到心脏表面，最终导致了几个必需的细胞成人心脏的类型包括心脏成纤维细胞和脉管系统的平滑肌细胞。这该建议的目的将利用我们一系列独特的技术，试剂和动物模型来阐明形成和功能所需的分子和细胞途径心外膜。这样，我们将提供一个研究心脏形成和止血的平台，以及因此，被证明是对人类先天性心脏病的机械洞察力。