Micro-Mechanical Role of Hypertension in Intimal Hyperplasia

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中的作用已被广泛接受。本提案的目的是建立一个有效的健康和高血压（作为内膜增生的机械刺激，IH）冠状动脉整个血管壁的微观结构模型。该方案涉及原位多光子显微镜（MPM），可以对机械载荷下冠状动脉的弹性蛋白、胶原蛋白和平滑肌细胞（SMC）进行三维描述，实验方法可以量化冠状动脉壁的分层结构，利用非线性力学的数值算法，以及现代计算能力来处理复杂的微观结构几何和边界条件。为此，本文的具体目标是：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Aim 1的全本构动脉壁模型

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.