Uncovering mechanisms behind long-term heart problems

27 November 2018

Heart attacks kill over 7 million people every year, and those who survive often go on to suffer from long term heart problems caused by the initial damage, and the heart muscle’s responses to it. Similar issues are also found in patients with high blood pressure. Dr Georgia Connolly has uncovered some of the molecular pathways that might be behind these long-term problems; it’s hoped that her findings might be extended to lead to new treatments.

The changes that heart attacks or high blood pressure can cause within the heart tissue include alterations to the size, mass, shape or function of the heart. These can make it less efficient at pumping blood, and the patient can display symptoms of heart failure. Dr Connolly used the Elizabeth Blackwell Institute Clinical Primer scheme to investigate some of the processes which might contribute to these issues.

Some of these changes can be caused by a process called cardiac fibrosis, or the build up of unwanted non-muscular tissue (including collagen) within the heart itself. Increased levels of a high-blood pressure causing hormone, angiotensin II (Ang II) might be involved in this, so with the help of Professor Sarah George, Dr Connolly looked at the different molecular signalling pathways within the cell that might be involved.

She found that the presence of Ang II increases the amount of collagen made by human cardiac fibroblasts (cells within the heart that - amongst other things - play a key role in wound healing), and in mice, Dr Connolly was able to identify the particular pathway - known as the Wnt signalling pathway that Ang II might use to effect this collagen production, and that it may be able to disrupt communication between cells.

Overall, Dr Connolly’s suggestion is that Ang II modulates the Wnt signalling pathway which may contribute to cardiac fibrosis. But the work on this topic is far from over; her work has lead to two MSc projects, one of which has recently converted to a PhD. A manuscript is also in preparation.

In working in a laboratory-based setting, Dr Connolly had to acquaint herself with a wide variety of in vitro and in vivo laboratory techniques, and the EBI Clinical Primer has been invaluable: “I was able to build on previous research experience and develop independence in numerous skills such as general laboratory skills, statistical analysis and scientific report generation. The clinical primer has confirmed my ambitions to be a clinical academic and has left me determined to pursue this as a career.”

And furthermore, she’s adamant that her overall experience, taking the EBI Clinical Primer part time, has allowed her to develop the flexibility needed to function in both clinical and research positions:

“It was a determining factor in my success in being awarded a NIHR funded Academic Clinical Fellowship to complete higher specialist training in Cardiology within the Severn Deanery. Alongside undertaking the primer part time, I spent the other half of my time completing a clinical fellowship at the Bristol Heart Institute and I really enjoyed balancing clinical and research roles."

Further information

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