Micro-Mechanical Role of Hypertension in Intimal Hyperplasia

高血压在内膜增生中的微机械作用

• 批准号: 8880455
• 负责人: GHASSAN S KASSAB
• 金额: $ 62.87万
• 依托单位: CALIFORNIA MEDICAL INNOVATIONS INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8880455
• 关键词: 3-Dimensional; Agreement; Algorithms; American; Animal Disease Models; Animal Model; Arterial Fatty Streak; Arteries; Atherosclerosis; Behavior; Biology; Biomechanics; Blood Vessels; Cardiovascular system; Cells; Clinical; Collagen; Collagen Fiber; Complex; Computer Simulation; Coronary; Coronary Arteriosclerosis; Coronary artery; Cytoskeleton; Data; Development; Economic Inflation; Elastin; Elastin Fiber; Elements; Environment; Extracellular Matrix; Fiber; Finite Element Analysis; Fluorescence; Foundations; Generations; Geometry; Health; Heart Diseases; Hyperplasia; Hypertension; Image; Imaging Techniques; In Situ; Laws; Literature; Measurement; Measures; Mechanical Stress; Mechanics; Methods; Microscopic; Microscopy; Modeling; Physiological; Population; Positioning Attribute; Process; Property; Research; Risk Factors; Role; Rupture; Smooth Muscle Myocytes; Spatial Distribution; Stimulus; Stress; Structural Models; Structure; Testing; Tissues; Torsion; Translations; Tunica Adventitia; Validation; atherogenesis; base; computer framework; experience; fiber cell; geometric structure; image processing; image reconstruction; intima media; mortality; multi-photon; novel; pressure; response; second harmonic; success; two-photon; virtual

DESCRIPTION (provided by applicant): The roles of mechanical stresses and strains in hypertension and atherogenesis are well accepted. The objective of this proposal is to develop a validated micro-structural model of the entire vessel wall of coronary arteries in health and hypertension (as a mechanical stimulus for intimal hyperplasia, IH). The proposal involves in situ Multi-Photon Microscopy (MPM) that enables the 3-D depiction of elastin, collagen and smooth muscle cells (SMC) of the coronary artery under mechanical loading, experimental approach to quantify the layered structure of the wall, numerical algorithm that takes advantage of nonlinear mechanics, and modern computational capability to deal with the complex micro-structural geometry and boundary conditions. Accordingly, the Specific Aims are: 1) To develop a passive and active constitutive model for coronary arterial wall based on constituent ultrastructure (fibers and SMC); 2) To validate the full constitutive arterial wall model of Aim 1 using both passive and active data of (macroscopic) triaxial mechanical tests and in situ imaging of the microstructural deformation; and 3) To elucidate the mechanical role of hypertension on IH using the validated models of Aim 2 combined with finite element analysis and experimental validation. We have previously established the methods of triaxial mechanical testing (inflation, extension and twist), in situ microstructure imaging, image processing and reconstruction, and developed a novel predictive micromechanics model of the adventitia. Here, we propose to extend these developments to the entire wall to provide a validated virtual vessel model that can be used to verify various hypotheses quantitatively (e.g., role of hypertension on IH). The success of the proposed microstructure-based computational framework will provide an accurate and reliable mathematical description of the structure-function relation of coronary arteries, and result in a new level of understanding for the mechanical response of the vessels. Furthermore, the extensive quantitative experimental data of the microstructures in health and hypertension (including IH) and their deformation will greatly enrich the understanding of the mechanical environment of the fibers and SMC and the remodeling process in atherogenesis.

描述（由申请人提供）：机械应力和应变在高血压和动脉粥样硬化形成中的作用已被广泛接受。该提案的目的是开发一个经过验证的健康和高血压状态下冠状动脉整个血管壁的微观结构模型（作为内膜增生的机械刺激，IH）。该提案涉及原位多光子显微镜 (MPM)，能够在机械负载下对冠状动脉的弹性蛋白、胶原蛋白和平滑肌细胞 (SMC) 进行 3D 描绘，通过实验方法量化冠状动脉壁的分层结构，数值模拟算法利用非线性力学和现代计算能力来处理复杂的微观结构几何和边界条件。 因此，具体目标是： 1）建立基于成分超微结构（纤维和SMC）的冠状动脉壁被动和主动本构模型； 2) 验证目标 1 的完整动脉壁模型 使用（宏观）三轴机械测试的被动和主动数据以及微观结构变形的原位成像； 3) 使用 Aim 2 的验证模型结合有限元分析和实验验证来阐明高血压对 IH 的机械作用。我们之前建立了三轴力学测试（膨胀、延伸和扭曲）、原位微观结构成像、图像处理和重建的方法，并开发了一种新型的外膜预测微观力学模型。在这里，我们建议将这些进展扩展到整个壁，以提供经过验证的虚拟血管模型，可用于定量验证各种假设（例如，高血压对 IH 的作用）。所提出的基于微观结构的计算框架的成功将为冠状动脉的结构功能关系提供准确可靠的数学描述，并使对血管机械响应的理解达到新的水平。此外，健康和高血压（包括IH）的微结构及其变形的广泛定量实验数据将极大地丰富对纤维和SMC的力学环境以及动脉粥样硬化形成中的重塑过程的理解。