Prenatal Load Mudulation of Cardiac Growth

心脏生长的产前负荷调节

• 批准号: 7298842
• 负责人: GEORGE D GIRAUD
• 金额: $ 18.73万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7298842
• 关键词: Adult; Affect; Anatomy; Blood flow; Cardiac; Cardiac Myocytes; Cardiac Output; Cardiovascular Physiology; Condition; Development; Elderly; Equilibrium; Fetal Growth; Fetal Heart; Fetoplacental Circulation; Fetus; Genetic; Goals; Growth; 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; Personal Satisfaction; Process; Process Measure; Proteins; Rate; 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; size

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成长对于不断增长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展和随后的成长有所了解，但 胎儿心脏生长的基础机制尚不清楚。我们的实验室有一个长期的 胎儿心脏生长中的疾病。我们发现在压力期间胎儿心脏功能有所不同 过载或音量过载。我们还发现，胎儿心肌细胞经历不同的发生率 终端分化时承受压力增加或体积负荷增加时。我们有 发现增生和肥大在不断增长的胎儿心脏中没有直接联系。 这些发现很重要，因为这些增长机制与成年人不同， 因为心脏使用解剖构型，所以它作为生命的胎儿发展。项目第二将进一步 通过追求以下特定目的来探索心脏功能与增长之间的关系： 特定目标1（心脏功能）：评估收缩负荷调制期间胎儿心血管功能 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 血液流向胎儿的全身和胎儿胎盘循环，以维持胎儿的健康。 特定目标2（心脏增长）：确定增生的相对贡献和时机 在收缩压负荷增加和收缩压负荷降低的条件下肥大。增长 胎儿心脏可能取决于肌细胞增生，肥大和末端的负载驱动的平衡 分化。 特定目标3（体内心肌肌细胞信号传导）：确定MAP激酶信号的作用 增生和肥大的级联反应增加或减少心脏负荷。心肌 将研究从暴露于正常，增加或减少收缩载荷的心脏的组织。机械负载 诱导的胎儿心脏生长可能是由MAP激酶信号级联反应介导的。 叠加在发展心脏腔形式的遗传指令上是血液动力学线索， 这决定了胎儿心脏的生长和功能的速度。了解心脏的机制 胎儿期间的生长和终端分化将为您提供重要的见解 病理生理过程影响后来的成人心脏。