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Atrial fibrillation: Investigating the impact of atrial fibrosis and atrial myopathy, from mouse to man


Institute of Ageing and Chronic Disease

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Dr Takao Sakai , Prof GYH Lip Applications accepted all year round Self-Funded PhD Students Only

About the Project

Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder, effecting 1-2% of the general population, which is characterised by a rapid and irregular heartbeat. It is associated with a number of serious complications including a four-fivefold increased risk of stroke and two- to threefold risk of heart failure. Atrial myopathy forms the substrate for AF and underlies the potential for atrial thrombus formation and subsequent stroke. Although the atrial substrate underlying AF is likely developing for years before the onset of AF, there is no current evaluation to identify and characterise preclinical atrial myopathy.

Fibrosis is an abnormal extension of the wound healing process that follows tissue damage, characterised by the excessive accumulation of collagenous extracellular matrices; it is involved in pathogenesis in a variety of chronic diseases. Our group has recently demonstrated that there are at least two independent mechanisms of major extracellular component type I collagen re-organisation following tissue/organ injury. Our overarching hypothesis is that the fibrosis is the key atrial substrate underlying AF. The aim of this project is to fully characterise how the fibrosis could contribute to the onset of AF.

In this project, we would like to pursue three main objectives.
Objective #1: To explore the dynamic changes of extracellular matrix components using aging mouse heart models.
Since the development of cardiac fibrosis is one of the hallmarks of cardiac aging and increases the risk of AF, we will investigate the dynamic changes of extracellular components using aging mouse models.

Objective #2: To characterize specific changes of extracellular matrix components and cardiac fibrosis in human AF patients.
Blood and tissue samples will be taken from the right or left atria during aortic valve- and mitral valve-replacement surgery respectively in AF patients. Using cardiac tissue samples, we will evaluate the extent of fibrosis, and characterise the component of extracellular matrices, and eventually the extent of formed fibril-stiffness in fibrotic tissues using histopathological, biochemical, and biomechanical approaches, compared to non-AF patients. The obtained results will be subsequently correlated to the imaging and blood biomarker data. We will address which type I collagen network formation-pathways will cause the disease progression.

Objective#3: To explore the relationships between cardiac surgery and post-operative AF.
We will examine blood and cardiac tissue from non-AF patients at cardiac surgery, and assess the relationship to the development of post-operative AF.

This is an exciting body of translational research and there is also scope for a dynamic and committed student to direct their research in different directions depending on their own interests and goals. The Liverpool Centre for Cardiovascular Science (LCCS) is an excellent multidisciplinary research environment with direct links to unique technological platforms and technical expertise, ideal for the student to learn valuable laboratory techniques and skills for their future career. There is an opportunity to join an AF research team that is globally recognised for AF research [ http://expertscape.com/ex/atrial+fibrillation].

We are looking for a highly motivated student who is willing to pursue cutting edge research within a vibrant and collegiate team. A basic background in cardiovascular science and histopathology would be beneficial.

Specific eligibility requirements:
Essential:
• BSc (minimum upper-second honors degree) in a related discipline.
• Excellent communication skills to patient and academic audience.
• Experience of quantitative physiological data collection.

For an informal discussion about this opportunity please email Dr Takao Sakai ([Email Address Removed]).

Applicants should send a CV (including two references), covering letter (2-page max), and the names of at least two references to Dr Takao Sakai directly ([Email Address Removed]). Please indicate your motivation for applying for the post and detail how your qualifications, skills and experience will contribute to the project.

Funding Notes

There is no funding attached to this PhD opportunity. Individuals with a scholarship or who are willing to self- fund are invited to apply for this PhD project. Fee information can be found on the University website.
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