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）：机械应力和菌株在高血压和动脉粥样硬化中的作用已得到充分接受。该提案的目的是开发健康和高血压冠状动脉壁的验证的微观结构模型（作为内膜增生的机械刺激，IH）。该建议涉及在机械载荷，实验性的方法下，可以对冠状动脉的弹性蛋白，胶原蛋白和平滑肌细胞（SMC）进行3-D描述，以量化墙壁的分层结构（数值算法），从而利用非线性机械师和界面的核心经验。 因此，具体目的是：1）基于组成型超微结构（Fibers and SMC）开发一个被动和主动的冠状动脉壁模型； 2）验证AIM的完整组成型动脉壁模型1 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的验证模型与有限元分析和实验验证相结合，阐明了高血压在IH上的机械作用。我们以前已经建立了三轴机械测试（通货膨胀，扩展和扭曲），原位微观结构成像，图像处理和重建方法，并开发了一种新颖的Addeditia预测微力学模型。在这里，我们建议将这些发展扩展到整个墙壁，以提供经过验证的虚拟血管模型，该模型可用于定量验证各种假设（例如，高血压在IH上的作用）。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，并为血管的机械响应提供新的了解水平。此外，健康和高血压微结构（包括IH）的广泛定量实验数据及其变形将极大地丰富对纤维和SMC的机械环境以及动脉粥样硬化过程中的重塑过程的理解。