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Title: Nanoscale characterisation of arterial stiffening
Author: Chang, Zhuo
ISNI:       0000 0004 7658 4743
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Arterial stiffening as part of the natural ageing process is strongly linked to cardiovascular risk. Although arterial stiffening is routinely measured in vivo, little is known about how localised changes in artery structure and biomechanics contribute to in vivo arterial stiffening. This is mainly due to the limitation of the conventional mechanical testing methods. To circumvent this challenge, a novel nano-scale structural and mechanical characterisation technique, known as PeakForce Quantitative Nanomechanical Mapping (QNM) technique, was developed in a zebrafish model. Using the zebrafish vertebral column, the utility of the PeakForce QNM for probing small-scale biological samples and structures was validated, which paved the way to probe human artery and investigate the localised alterations in artery structure in vitro with arterial stiffening. Human internal mammary artery (IMA) was used as a model vessel for understanding the development of arterial stiffening in this thesis. This thesis focuses on the role of the tunica media and the outmost layer, the tunica adventitia, in arterial stiffening. Using the PeakFoce QNM, the hydrated and dehydrated arterial sections were tested that provided data on nano-scale changes in collagen fibril structure and mechanical properties in the hydrated media, dehydrated media and adventitia and showed how they related to in vivo stiffness measurements in the vascular system. The indentation depth for AFM measurement on the IMA tissues of 5 μm thickness were controlled at 20 nm and 5 nm in liquid and ambient conditions respectively and thus the indentation depth/tissue thickness ratio was 0.4% and 0.1% for the hydrated and dehydrated samples respectively. Furthermore, integrating the findings in this thesis with the proteome analysis data, the localised alterations in the collagen and ultrastructure were explained, and the in vivo arterial stiffening, nanomechanical and structural changes in artery biopsy samples were linked. This approach could be used to develop new diagnostic methods for vascular disease.
Supervisor: Akhtar, Riaz ; Paoletti, Paolo ; Chen, Po-Yu Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral