Mechanical Factors in Maturation of the Large Artery Wall

大动脉壁成熟的机械因素

基本信息

批准号：
1662434
负责人：
Jessica Wagenseil
金额：
$ 40万
依托单位：
Washington University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1662434&HistoricalAwards=false
关键词：
Mechanical Factors Maturation Large Artery

项目摘要

The large arteries are composed of smooth muscle cells surrounded by an extracellular matrix that provides reversible elasticity. The arterial wall distends when blood is pumped out as the heart contracts, and then returns the stored energy as the heart relaxes, dampening the pulsatile pressure wave from the heart and providing continuous blood flow to distal vessels. This dampening behavior is known as the Windkessel function and when it is compromised, there are negative effects on downstream organs such as the kidneys, heart, and brain. Maturation of the arterial wall, specifically deposition of elastic fibers in the extracellular matrix, is critical for the Windkessel function. The overall goal of this research program is to determine how hemodynamic forces during embryonic development drive elastic fiber assembly and overall arterial wall maturation. The results of the research may be used to optimize clinical interventions or tissue engineering protocols that encourage proper temporal and spatial expression of extracellular matrix proteins and smooth muscle cell differentiation necessary for the Windkessel function. To date, there are no clinical interventions that can repair the Windkessel function in arterial disease or replicate the Windkessel function in tissue-engineered arterial replacements. The project will also have broader impacts through training students in research methods, exposing students to the unique growth and remodeling behavior of arteries, and introducing middle school students to engineering topics.It is generally accepted that mechanical factors, such as blood pressure and flow, influence the form and function of developing arteries, but little of the previous work has focused on the time period of arterial wall maturation. However, the maturation process is critical for the arterial Windkessel function. This project will use chick embryos to take advantage of the physical manipulation of cardiovascular hemodynamics and imaging throughout development that is uniquely possible in the chick. The role of hemodynamic forces in arterial wall maturation will be investigated through quantification of normal arterial wall maturation in the chick; quantification of altered arterial wall maturation in the chick caused by changes in blood flow and/or pressure and the resulting shear and circumferential wall stresses due to ligation of the vitelline vein; and by integrating the experimental data into a biomechanical model of arterial wall maturation that can be used for identifying critical parameters in the maturation process that may be important for clinical applications.

大动脉由平滑肌细胞组成，这些平滑肌细胞被提供可逆弹性的细胞外基质。当心脏收缩时血液泵出血液时，动脉壁会膨胀，然后随着心脏放松而恢复储存的能量，从心脏中抑制脉冲压力波，并将连续的血液流向远端血管。这种衰减行为被称为Windkessel功能，当它被妥协时，会对肾脏，心脏和大脑等下游器官产生负面影响。动脉壁的成熟，特别是弹性纤维在细胞外基质中的沉积，对温克塞尔功能至关重要。该研究计划的总体目标是确定胚胎发育过程中的血液动力学如何驱动弹性纤维组件和整体动脉壁成熟。该研究的结果可用于优化临床干预措施或组织工程方案，这些方案鼓励临时和空间表达细胞外基质蛋白以及Windkessel功能所需的平滑肌细胞分化。迄今为止，尚无临床干预措施可以修复动脉疾病中的Windkessel功能或复制组织工程动脉替代物中的Windkessel功能。该项目还将通过培训学生进行研究方法，使学生了解动脉的独特成长和重塑行为，并将中学生引入工程主题，从而产生更广泛的影响。人们普遍认为，机械因素（例如血压和流动），例如血压和流动，影响了动脉的形式和功能，但前一项工作的几乎没有集中于既有壁墙的时间范围的时间段。但是，成熟过程对于动脉Windkessel功能至关重要。该项目将使用雏鸡胚胎利用在整个发育过程中对心血管血流动力学和成像进行的物理操纵，这在小鸡中是独特的。血流动力在动脉壁成熟中的作用将通过定量雏鸡中的正常动脉壁成熟来研究。由于血流变化和/或压力的变化以及由于卵黄静脉的连接而导致的剪切和圆周壁应力引起的雏鸡中动脉壁成熟的改变；通过将实验数据整合到动脉壁成熟的生物力学模型中，该模型可用于识别成熟过程中的关键参数，这对于临床应用可能很重要。