Mechanical Signals in Vessel Development

船舶开发中的机械信号

• 批准号: 7760875
• 负责人: Jessica Wagenseil
• 金额: $ 24.9万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7760875
• 关键词: A Mouse; Adult; Affect; Animals; Architecture; Biomechanics; Biomedical Engineering; Blood; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cellular biology; Characteristics; Collagen; Communication; Data; Development; Disease; Educational process of instructing; Elastin; Extracellular Matrix Proteins; Gene Expression; Growth; Human; Hypertension; Knowledge; Laboratories; Life; Longevity; Measures; Mechanical Stress; Mechanics; Mentorship; Modeling; Mus; Patients; Physiology; Play; Principal Investigator; Process; Proteins; Radial; Recruitment Activity; Research; Research Training; Role; Saints; Signal Transduction; Smooth Muscle Myocytes; Staging; Stimulus; Stress; Structure; Supravalvular aortic stenosis; System; Testing; Training; Universities; Washington; base; career; hemodynamics; mathematical model; mature animal; mechanical behavior; meetings; mouse model; predictive modeling; pressure; professor; programs; skills; tool; treatment strategy

This proposal outlines a three year program of research and training td establish the principal investigator (PI) as a biomedical engineering professor studying develqpmeiital cardiovascular mechanics. A postdoctoi-al year has been completed In Dr. Robert Mecham's laboratory at Washington University, where the PI expanded her knowledge of cell biology and physiology and practiced communication and management skills. The PI has accepted a tenure-track assistant professorship at Saint Louis University and plans to continue'her previous research. She will establish her independence by combining the cell biology and physiology with her expertise in biomechanics and mechanical modeling. Career training w/lir include teaching, mentorship by established professors and exposure at national meetings: During cardiovascular development, blood pressure and flow increase and smooth muscle cells produce extracellular matrix proteins, such as collagen and elastin. that define the mechanical behavior of the vessel wall. A mouse .model o( supravalvular aortic stenosis, an elastin-associated disease in humans, showed that elastin haploinsufficiency (eln+/-) results in altered vessel wall structure, decreased compliance and Increased blood pressure. Despite these features. eInW- mice live a normal life span, suggesting that they adjust to reduced elastin amounts and the resulting changes Iri rriechanicat stimuli. The hypothesis of this proposal is that developing vessels remodel to optimize mechanical stresses in the wall and that these stresses, provide a key signal for cellular differentiation. This remodeling will be described and predicted by a mathematical model in which pertiirbations cause grovi/th of various components, returning the stresses near homeostatic values. Because of the unique developmental remodeling in the eln+/-.cardiovascular system, these mice provide an Ideal tool to investigate the hypothesis and validate the mechanical model. The specific aims are: 1) To detennine hemodynamic, mechanical and geometric parameters In developing vessels. 2) To determine how changes in elastin amount alter mechanical sigriats in developing vessels. 3) To develop a constrained mixture model lo predict the growth of developing vessels.

该提案概述了三年的研究和培训计划，建立了校长 研究人员（PI）是研究Develqpmeiital心血管机械的生物医学工程教授。 在华盛顿大学的罗伯特·梅切姆（Robert Mecham）博士的实验室已经完成了博士后一年 PI扩大了她对细胞生物学和生理学的了解，并实践了交流和 管理技能。 PI接受了圣路易斯大学的终身助理教授职位 并计划继续以前的研究。她将通过组合牢房来建立自己的独立性 生物学和生理学及其在生物力学和机械建模方面的专业知识。带LIR的职业培训 包括教学，既定教授的指导以及在国家会议上的接触： 在心血管发育期间，血压和流动增加以及平滑肌细胞 产生细胞外基质蛋白，例如胶原蛋白和弹性蛋白。这定义了机械行为 船墙。小鼠.Model O（卵形主动脉狭窄，一种与弹性蛋白相关的疾病，人类，表明弹性蛋白单倍不适（ELN +/-）导致血管壁的结构改变，依从性降低和血压升高。尽管有这些特征。尽管这些特征是正常的寿命，表明它们会降低弹性蛋白的元素，并降低了弹性蛋白的效果。该提议的假设是，开发容器重塑，以优化壁中的机械应力，这些应力为细胞分化提供了关键的信号，将通过数学模型来描述和预测，其中pertiirbations grovi grovi grovi grovi grovi grovi/the shove servien+bervience the+berde servien+bery selov inder servience intos selov repress the+the+the+thei+the+the+。研究假设并验证机械模型的理想工具。 具体目的是：1）发育中的血管中发出血液动力学，机械和几何参数。 2）确定弹性蛋白量的变化如何改变发育中的血管中的机械临床。 3）开发约束的混合模型，可以预测发育中的血管的生长。