Bio-mechanical studies of normal and aging arterial wall

正常和老化动脉壁的生物力学研究

• 批准号: RGPIN-2019-07178
• 负责人: DiMartino, Elena
• 金额: $ 2.33万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739344
• 关键词: Bio; mechanical; studies; normal; aging

The aorta is the largest vessel in the body, exiting the heart and carrying oxygen-rich blood to cells in all other regions of the anatomy. Essentially, the aorta is a cylindrical tube with smooth walls and is extremely strong. Yet, it starts losing strength with age. This is associated with an overall decrease of the tissue organization with loss of elastin, which is the primary load bearing element, along with an increase of other less desirable components. The proposed research will answer the following fundamental questions: (a) how do we monitor the properties (for example stiffening) of blood vessels across the lifespan? (b) can we develop methods to estimate these properties from images without the need for actual mechanical tests? and (d) what are the molecular processes that occur in arterial tissues as they age, and can they be `recognized' from their imaging and flow signatures? The specific five-year objectives are as follows: 1.Develop and test a new mathematical model for healthy arterial tissue that describes changes due to growth (remodelling) and aging. 2.Develop techniques to estimate local arterial wall stiffness - by properly linearizing the constitutive model - and flow patterns, in vivo. 3.Study cell signalling and inflammatory processes which are part of the physiological remodelling processes in healthy arterial tissues. The advantage of this research is that it will make it possible to follow changes in the properties of healthy arteries. Most healthy tissues cannot be obtained from the general population and the amount and quality of tissues obtained from autopsy is limited. Therefore non-invasive techniques offer a unique opportunity. Moreover, current methodologies that monitor stiffening of arteries (for example pulse-wave velocity) do not link them to the micro-structural components and do not allow assessment of the in vivo stretch. This is important because higher pressure may manifest itself as increased apparent stiffness without changes in the tissue property. A new constitutive model capable of describing both remodelling and aging will be proposed and applied. Outcomes will be atlases of normal and aging aortas which could be used to achieve early diagnoses and eventually prioritize treatment options. This project will prepare undergraduate, graduate and post-doctoral trainees in interdisciplinary research. The students will build expertise in mathematical modelling, non-linear mechanics, fluid mechanics, biology, microscopy and statistical methodologies. They will build knowledge at the boundaries of engineering and natural science with a strong focus on critical thinking. These skills are translatable in many disciplines both in the area of bioengineering, as well as outside, in composite mechanics and polymeric material science, for example.

主动脉是人体最大的血管，离开心脏并将富氧血液运送到解剖结构的所有其他区域中的细胞。从本质上讲，主动脉是一个圆柱形的管壁光滑，非常强大。然而，随着年龄的增长，它开始失去力量。这与组织结构的总体减少以及作为主要承重元件的弹性蛋白的损失以及沿着的其它不太期望的组分的增加有关。拟议的研究将回答以下基本问题：（a）我们如何在整个生命周期内监测血管的特性（例如硬化）？(b)我们能不能开发出不需要实际的机械测试就能从图像中估计这些特性的方法？以及（d）随着年龄的增长，动脉组织中发生了哪些分子过程，它们能否从成像和血流特征中“识别”出来？具体的五年目标如下：1.开发和测试一个新的健康动脉组织的数学模型，该模型描述了由于生长（重塑）和衰老而引起的变化。2.开发技术来估计局部动脉壁刚度-通过适当线性化的本构模型-和流动模式，在体内。3.研究细胞信号传导和炎症过程，这是健康动脉组织生理重塑过程的一部分。 这项研究的优点是，它将使人们有可能跟踪健康动脉特性的变化。大多数健康组织不能从普通人群中获得，从尸检中获得的组织的数量和质量都是有限的。因此，非侵入性技术提供了一个独特的机会。此外，目前监测动脉硬化的方法（例如脉搏波速度）没有将它们与微结构部件联系起来，并且不允许评估体内拉伸。这是重要的，因为较高的压力可以表现为增加的表观硬度而不改变组织性质。一个新的本构模型能够描述重塑和老化将被提出和应用。其结果将是正常和老化的乳腺癌的地图集，可用于实现早期诊断，并最终优先考虑治疗方案。该项目将培养跨学科研究的本科生、研究生和博士后学员。学生将建立数学建模，非线性力学，流体力学，生物学，显微镜和统计方法的专业知识。他们将在工程和自然科学的边界上建立知识，并重点关注批判性思维。这些技能在生物工程领域以及复合材料力学和聚合物材料科学等领域的许多学科中都是可翻译的。