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Cascading failure of the aorta - The role of collagen degradation in the development of aortic dissection


   Department of Mechanical, Aerospace & Materials Engineering

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  Dr R Akhtar, Dr J Madine  No more applications being accepted  Self-Funded PhD Students Only

About the Project

The aorta is the largest conduit for blood flow in the human body and vital for cardiovascular health. Aortic dissection (AD) occurs when there is a split in the wall of the aorta, resulting in the creation of an artificial channel for blood flow, which can lead to rupture. AD is a devastating, life-threatening condition which is associated with a high mortality rate often in young patients with no prior relevant medical history.

The properties of the aorta are governed by its extracellular matrix (ECM) components, in particular, collagen, elastin and glycosaminoglycans. There is still a lack of understanding about the underlying mechanisms that lead to AD. A concerted effort is needed to better understand the role of different ECM components in the development and propagation of AD. A recent numerical modelling study has suggested that a local build-up of strain energy followed by a cascade failure of inhomogeneously distributed interlamellar collagen fibres can be implicated in the development of AD [1]. This fits with research which has demonstrated the link between that fluoroquinolones, a widely used class of antibiotics, and the development of aortic dissection [2]. Fluoroquinolones are linked to collagen degradation and this further highlights the role of collagen in AD development. 

The objective of this inter-disciplinary PhD project is to investigate the role of collagen degradation in the development of, and progression of AD. The specific objectives of this PhD are:

-      To develop an in vitro model for AD and explore the role of collagen degradation

-      To characterise the nano- and micro-scale structural organisation of collagen fibres in AD tissue.

-      To relate structural and biomechanical properties in dissected aortic tissue.

In this project, a number of high spatial resolution techniques will be applied to study multi-scale structural features and mechanical properties of aortic tissue. To determine topographical and biomechanical alterations in AD, we will employ advanced atomic force microscopy (AFM) based PeakForce Quantitative Nanomechanical Mapping (PFQNM) technique to investigate nano-scale changes associated with collagen-degradation. PFQNM enables the co-localization of ultrastructural and mechanical properties with a high resolution. Optical microscopy, SEM and TEM will be utilized to observe the nano-/micro-structure of the aorta, focusing on collagen fibril organization..

This will not only aid understanding of the mechanisms that lead to the development of aortic dissection, hence enabling the development of therapeutics but also result in better approaches for antibiotic use.

The successful candidate will join the LABB Group (Liverpool Aortic Biomechanics and Biochemistry Research Group), www.labb-group.com, a multidisciplinary group with expertise in aortic biomechanics, biochemistry and surgery. The LABB group has members from University of Liverpool, Royal University Liverpool Hospital and Liverpool Heart and Chest Hospital. 

For any enquiries, please contact Dr Riaz Akhtar on: [Email Address Removed]

To apply for this opportunity, please visit: https://www.liverpool.ac.uk/study/postgraduate-research/how-to-apply/ and click the 'Ready to apply? Apply now' button.


Funding Notes

This project is for self-funded students only, for example, through government-awarded scholarships. Tuition fees can be found on the following page: https://www.liverpool.ac.uk/study/postgraduate-research/fees-and-funding/fees-and-costs/
Bench fees will be £4000 per annum.

References

[1] Xunjie et al., Avalanches and power law behavior in aortic dissection propagation. Science Advances 6.21 (2020): eaaz1173.
[2] Dong et al., Association of Infections and Use of Fluoroquinolones with the Risk of Aortic Aneurysm or Aortic Dissection. JAMA Intern Med. 2020;180(12):1587–1595.
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