Prenatal Load Mudulation of Cardiac Growth

心脏生长的产前负荷调节

• 批准号: 7858228
• 负责人: GEORGE D GIRAUD
• 金额: $ 20.46万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7858228
• 关键词: Adult; Affect; Anatomy; Blood flow; Cardiac; Cardiac Myocytes; Cardiac Output; Cardiovascular Physiology; Development; Elderly; Equilibrium; Fetal Heart; Fetoplacental Circulation; Fetus; Genetic; Goals; Growth; Growth and Development function; Health; Heart; Hyperplasia; Hypertrophy; Instruction; Laboratories; Left; Left ventricular structure; Life; Link; MAP Kinase Modules; Magnetic Resonance Imaging; Measurement; Mechanics; Mediating; Messenger RNA; Microscopic; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Muscle Cells; Myocardial; Myocardial tissue; Pathway interactions; Process; Process Measure; Proteins; Relative (related person); Role; Sheep; Signal Transduction; Sirolimus; Stress; Stroke Volume; Structure; Systolic Pressure; Techniques; Testing; Thick; Time; U-0126; Ventricular; computerized data processing; fetal; heart function; hemodynamics; human FRAP1 protein; in vivo; insight; prenatal; pressure; prevent; response

The proper development and growth of the fetal heart is essential to the health of the growing fetus. Even though we have some understanding of the development and subsequent growth of the mammalian heart, the mechanisms underlying fetal cardiac growth are not well understood. Our laboratory has a long-standing nterest in fetal cardiac growth. We have found that fetal cardiac function is different during pressure overload or volume overload. We have also found that fetal cardiac myocytes undergo different rates of terminal differentiation when exposed to increased pressure or to increased volume load. We have discovered that hyperplasia and hypertrophy are not directly temporally linked in the growing fetal heart. These discoveries are important because these growth mechanisms are different from those of the adult and because the heart uses the anatomic configuration it develops as a fetus for life. Project II will further explore the relationship between cardiac function and growth by pursuing the following Specific Aims: Specific Aim 1 (Cardiac Function): to assess fetal cardiovascular function during systolic load modulated growth. Functional adaptation of the fetal heart to systolic load likely allows the fetus to maintain adequate blood flow to the fetal systemic and fetal placental circulations maintaining the well being of the fetus. Specific Aim 2 (Cardiac Growth): to determine the relative contribution and timing of hyperplasia and hypertrophy in conditions of increased systolic pressure load and reduced systolic pressure load. Growth of the fetal heart is likely dependent on a load driven balance of myocyte hyperplasia, hypertrophy and terminal differentiation. Specific Aim 3 (In Vivo Cardiac Myocyte Signaling): to determine the role of the MAP Kinase signaling cascade in hyperplasia and hypertrophy in response to increased or decreased cardiac load. Myocardial tissue from hearts exposed to normal, increased or decreased systolic load will be studied. Mechanical load induced fetal cardiac growth is likely mediated by the MAP kinase signaling cascade. Superimposed on the genetic instructions for developing cardiac chamber form are hemodynamic clues, which determine the rate of growth and function of the fetal heart. Understanding the mechanisms of cardiac growth and terminal differentiation during the fetal period will provide important insight into the pathophysiological processes affecting the adult heart in later life.

胎儿心脏的正常发育和生长对于成长中的胎儿的健康至关重要。甚至 尽管我们对哺乳动物心脏的发育和随后的生长有一些了解， 胎儿心脏生长的机制尚不清楚。我们的实验室拥有长期 对胎儿心脏生长的兴趣。我们发现胎儿心脏功能在压力过程中是不同的 超载或容量超载。我们还发现胎儿心肌细胞经历不同速率的 当暴露于增加的压力或增加的容量负荷时，终末分化。我们有 发现在生长的胎儿心脏中，增生和肥大在时间上没有直接联系。 这些发现很重要，因为这些生长机制不同于成人和成人的生长机制。 因为心脏终生使用胎儿时发育的解剖结构。项目二将进一步 通过追求以下具体目标来探索心脏功能与生长之间的关系： 具体目标 1（心脏功能）：评估收缩负荷调节期间的胎儿心血管功能 生长。胎儿心脏对收缩负荷的功能适应可能使胎儿保持足够的收缩负荷 血液流向胎儿全身和胎儿胎盘循环，维持胎儿的健康。 具体目标 2（心脏生长）：确定增生和心脏生长的相对贡献和时间。 在收缩压负荷增加和收缩压负荷减少的情况下出现肥大。的成长 胎儿心脏可能依赖于负荷驱动的肌细胞增生、肥大和终末期的平衡 差异化。 具体目标 3（体内心肌细胞信号转导）：确定 MAP 激酶信号转导的作用 增生和肥大级联反应响应心脏负荷的增加或减少。心肌 将研究暴露于正常、增加或减少的收缩负荷的心脏组织。机械负载 诱导胎儿心脏生长可能是由 MAP 激酶信号级联介导的。 叠加在发育心室形态的遗传指令上的是血流动力学线索， 它决定胎儿心脏的生长速度和功能。了解心脏的机制 胎儿期的生长和终末分化将为了解 影响成年后心脏的病理生理过程。