Molecular networks of epicardial formation and function

心外膜形成和功能的分子网络

• 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
• 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

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.

摘要