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.

Public Health Relevance

The microstructures of the coronary arteries are important for understanding coronary artery disease initiation and progression in hypertension which is a major cause of mortality in the US. The objective of this proposal is to elucidate the relation between microstructure of the vessel wall and the macro-mechanical properties in order to understand the role of hypertension in atherogenesis.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VH-J (02))
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Lee, Albert
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California Medical Innovations Institute
San Diego
United States
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Guo, Xiaomei; Lu, Xiao; Yang, Junrong et al. (2014) Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats. Am J Physiol Heart Circ Physiol 307:H880-7
Chen, Huan; Luo, Tong; Zhao, Xuefeng et al. (2013) Microstructural constitutive model of active coronary media. Biomaterials 34:7575-83