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Biomechanical characterization of the remodeling of atherosclerotic arteries and plaque rupture

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thesis
posted on 28.03.2022, 23:45 by Alireza Rezvani Sharif
Myocardial infarction is one of the leading causes of death in the world, resulting mostly from the sudden rupture of atherosclerotic plaques. Atherosclerotic plaques often form in specific regions within the arterial tree characterized by complex blood flow patterns. The progression of initial plaques depends on arterial wall remodeling defined as any persistent changes within the composition and size of the artery allowing adaptation to new circumstance. Plaques that are prone to rupture may often be clinically silent until the time of rupture; hence, the detection of vulnerable plaques is of great importance. It has been hypothesized that mechanical fatigue caused by pulsatile blood pressure is the main mechanism underlying atherosclerotic plaque rupture. This thesis aimed to characterise the remodeling and rupture of atherosclerotic plaques from a mechanical perspective. For the characterization of remodeling of atherosclerotic arteries, the alteration of composition and geometry of atherosclerotic arteries were examined separately. To analyse the modification of mechanical properties of atherosclerotic lesion components with plaque development, 20 human abdominal aortas, and 20 human coronary arteries were extracted at autopsy from subjects who died mostly due to post-accident complications. The force-spectroscopy mode of the atomic force microscopy (AFM) and histological examination were used to determine the elastic moduli of specified locations within samples. To investigate the leading causes of expansive remodeling of atherosclerotic arteries, as well as its consequences, many idealised models mimicking different stages of plaque development were designed. Using fluid-solid interaction analysis, the distribution of mechanical stresses among different models was estimated and the results were compared. For the mechanical characterization of plaque rupture, the geometry of atherosclerotic coronary plaques was reconstructed from histological images. Pulsatile blood pressure was considered as the external load and stress distribution within each model was estimated using finite element method. The process of mechanical fatigue failure within atherosclerotic plaques was simulated based on fracture mechanics roles. Then, the effect of plaque morphology, mean and pulse blood pressure and lipid pool stiffness on the number of fatigue cycles required for the fracture of atherosclerotic plaques was investigated. The outcomes of the AFM test on the atherosclerotic abdominal aorta and coronary arteries indicated the high variability of Young's modulus at different locations of plaque. Fibrous cap showed a lower stiffness than the fibrous tissue beneath the lipid pool. Calcification zones and lipid pools were the stiffest and softest components of atherosclerotic lesions respectively. With atherosclerotic plaque development, reduction of elastin lamellae stiffness, as well as stiffening of inter-lamellar zones, were detected in the medial layer of the diseased portion of the abdominal aortic wall. Moreover, the increase of media stiffness due to the build-up of fibrosis tissue and reduction of the elastic modulus of internal elastic lamina was observed in coronary arteries. Significant differences were observed between the stiffness of the medial layer in diseased parts and free-plaque segments in incomplete plaques. The results of computational modeling on the remodeling of atherosclerotic arteries showed that in atherosclerotic plaques with expansive remodeling, the level of endothelial shear stress, as well as the level wall circumferential stress in the diseased-free wall of the artery, remain approximately in the physiological range. However, higher levels of stress are induced at the shoulder and cap of plaques with expansive remodeling compared to atherosclerotic plaques which do not exhibit remodeling. With the numerical simulation of fatigue failure of atherosclerotic plaques, it was found that the required time for the plaque rupture decreased with increase of mean and pulse pressure and with reduction of lipid pool stiffness. Development of atherosclerotic plaques leads to alteration of micromechanical properties of the arterial wall in both elastic and muscular arteries. Findings suggest that most atherosclerotic arteries exhibit expansive remodeling to preserve the normal level of mechanical stresses sensed by endothelial and smooth muscles cells. The increase of pulse and mean blood pressure, intensification of stiffness mismatch between plaque components, as well as the expansive remodeling of atherosclerotic arteries, can increase the risk of plaque rupture.

History

Table of Contents

Chapter 1. Introduction -- Chapter 2. Literature reviews -- Chapter 3. Mechanical characterization of the lamellar structure of human abdominal aorta in the development of atherosclerosis : an atomic force microscopy study -- Chapter 4. Progressive changes of elastic moduli of arterial wall and atherosclerotic plaque components during plaque development in human coronary arteries -- Chapter 5. Arterial wall remodeling in the development of atherosclerotic plaques: mechanical stress analys -- Chapter 6. Stress analysis of fracture of atherosclerotic plaques : crack propagation modeling -- Chapter 7. Conclusions, limitations and future directions -- Appendices -- References.

Notes

Empirical thesis. Bibliography: pages 140-152

Awarding Institution

Macquarie University

Degree Type

Thesis PhD

Degree

PhD, Macquarie University, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences

Department, Centre or School

Department of Biomedical Sciences

Year of Award

2019

Principal Supervisor

Alberto Avolio

Additional Supervisor 1

Mark Butlin

Additional Supervisor 2

Mohammad Tafazzoli-Shadpour

Rights

Copyright Alireza Rezvani Sharif 2018. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (xxi, 152 pages) illustrations (some colour)

Former Identifiers

mq:72159 http://hdl.handle.net/1959.14/1281983