Effects of Immediate Biochemcial Environments on the Structure and Function of Aortic Elastin

直接生化环境对主动脉弹性蛋白结构和功能的影响

• 批准号: 1100791
• 负责人: Yanhang Zhang
• 金额: $ 37万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1100791&HistoricalAwards=false
• 关键词: Effects; Immediate; Biochemcial; Environments; Structure

The research objective of this award is to study the structural and functional changes of elastin due to in vitro elastin lipid interactions and glycation. As one of the major structural proteins of the body, elastin is essential to accommodate physiological deformation and provide elastic support for blood vessels. Elastin is remarkably long lived, but it can suffer damage from the cumulative effects of chemical exposure. End products or side chain modifications resulting from elastin lipid interactions and glycation compromise the mechanical properties of elastin by altering elastin's mobility. Changes in the elastic and viscoelastic properties of aortic elastin due to the effects of immediate biochemical environments will be studied. The molecular basis of possible intra- and extrafibrillar compartment changes will be explored using Raman and FT-IR microspectroscopy. A multi-scale mechanobiological constitutive model will be created to incorporate the effects of mechanical loading and biochemical environment in predicting the macroscopic elastic and viscoelastic properties of elastin. Results from these studies will advance our understanding of the role of elastin mechanics in vascular remodeling. Changes in the mechanical properties of elastin have important medical and physiological consequences. Many pathological conditions involve significant remodeling of elastin and thus altered mechanical and physiochemical functions of tissues. Knowledge of the relationship between molecular level alterations and elastin's mechanical functionality is integral to understanding its performance in living biological systems. The broad interdisciplinary nature of this project will greatly benefit the undergraduate/graduate students trained through this project. Research results will be disseminated through journal publications and conference presentations, and will also be incorporated into undergraduate/graduate teaching. We plan to integrate several engineering activities into the outreach programs at Boston University. The goal is to help young women students build self-confidence and a love for science and engineering.

该奖项的研究目标是研究由于体外弹性蛋白脂质相互作用和糖化而导致的弹性蛋白的结构和功能变化。弹性蛋白是人体的主要结构蛋白之一，对适应生理变形和为血管提供弹性支撑至关重要。弹性蛋白的寿命非常长，但它可能会受到化学暴露的累积效应的损害。由弹性蛋白脂质相互作用和糖基化引起的终产物或侧链修饰通过改变弹性蛋白的流动性而损害弹性蛋白的机械性质。将研究由于直接生物化学环境的影响而引起的主动脉弹性蛋白的弹性和粘弹性性质的变化。可能的内和外原纤维室的变化的分子基础将探讨使用拉曼和傅立叶变换红外显微光谱。一个多尺度的力学生物本构模型将被创建，将机械载荷和生化环境的影响，在预测的宏观弹性和粘弹性弹性蛋白。这些研究的结果将促进我们对弹性蛋白力学在血管重塑中的作用的理解。弹性蛋白的机械性质的变化具有重要的医学和生理后果。许多病理状况涉及弹性蛋白的显著重塑，从而改变组织的机械和生理化学功能。分子水平的改变和弹性蛋白的机械功能之间的关系的知识是不可或缺的，以了解其在活的生物系统中的性能。该项目广泛的跨学科性质将大大有利于通过该项目培养的本科生/研究生。研究成果将通过期刊出版物和会议报告传播，并将纳入本科/研究生教学。我们计划将几项工程活动整合到波士顿大学的外展计划中。其目标是帮助年轻女学生建立自信和对科学和工程的热爱。