Pressure and Flow Induced Remodeling of Coronary Artery

University Of California Irvine, Irvine CA

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Abstract

DESCRIPTION (provided by applicant): The study of adaptation mechanisms in structure and function of blood vessels in response to physical stress is important in human health and disease. The objective of this proposal is to gain a better understanding of the adaptation mechanisms in the structure, mechanical properties and function of the coronary arteries to altered mechanical forces, including principal and shear stresses, in experimental models of hypertension and flow-overload, respectively. The effects of increased pressure and flow will be examined separately by studying the right coronary artery in aortic and pulmonary banding, respectively. The specific aims are: 1) To measure and state the physical loading acting on the blood vessels precisely and analytically with the nonstationary, nonlinear, and stochastic features taken into account; 2) To study the morphometric remodeling of coronary arterial blood vessels in vivo during the progression of hypertension and/or fiow-overload; 3) To determine the stress-strain relationship and the stress-tissue remodeling relationship in response to hypertension and/or flow-overload; 4) To study the remodeling of the three-dimensional structure of elastin and collagen under the various mechanical loadings prescribed in Aim 3 in unfixed, unstained tissue; and 5) To study the dynamics, linearity, superposability and non-linearity of the changes of morphometry and mechanical properties of Aims 2 and 3 in response to the dynamic changes of the magnitude and direction of the loading in Aim 1. The recorded in vivo blood pressure and flow data will be characterized with the intrinsic mode function method. The time course of change of blood vessel diameter, length and volume will be measured using digital subtraction angiography and video densitometery. The remodeling of the mechanical properties of coronary arteries will be measured in circumferential distension, longitudinal extension and torsion using a tri-axial machine. The changes in collagen and elastin fibers will be visualized with multi-photon microscopy. This research will clarify the role played by increased flow and pressure on coronary blood vessel remodeling by expressing the results mathematically in terms of indicial response functions and by using these functions to clarify the structural and mechanical remodeling that signifies hypertension and hypertrophy as important risk factors for coronary artery disease.