Tag: bhi

BHI scientist wins national science image contest with heart vessel image

Posted on by Rachel Skerry
Recreating heart blood vessels
Recreating heart blood vessels. Image credit : Dr Elisa Avolio

A scientist from the Bristol Heart Institute has won the British Heart Foundation’s (BHF) annual ‘Reflections of Research’ image competition. Where science and art collide, the competition challenges BHF-funded scientists to showcase their state-of-the-art heart and circulatory disease research through the generation of captivating images.

Dr Elisa Avolio’s entry ‘recreating heart blood vessels’ was chosen as this year’s judges’ winner. Although at first glance it appears to resemble a luminous jelly fish, the image shows new blood vessel-like structures – pictured in green in the centre – sprouting from a 3D gel.

Dr Avolio of the Bristol Medical School created the structures using a mixture of two types of heart cells – cardiac endothelial cells, which line the inside of every blood vessel, and pericytes, which ‘hug’ the outside of blood vessels to support the vessel and help it function.

During a heart attack, the arteries that supply blood to the heart are blocked, cutting off blood flow. The area of the heart starved of blood and oxygen dies, and it no longer functions to help the heart pump blood around the body. Dr Avolio is researching ways to encourage the formation of new blood vessels to replace those that have died, to restore blood supply to damaged areas of the heart.

Dr Avolio, a post-doctoral research associate, said:

“It is fantastic to have won this year’s Reflections of Research competition. Each year the entries display such variety in the BHF’s work to support heart and circulatory disease research.

“By recreating models of the heart blood vessels, we can see how the cells in blood vessel walls interact with and talk to other cells. This knowledge, along with understanding what molecules promote or block the formation of blood vessels, could be used in the future to develop new treatments for patients after a heart attack.”

Dr Neil Dufton, Lecturer in Inflammatory Sciences at Queen Mary University of London, was this year’s guest judge. He said:

“All of the images shortlisted in this year’s competition offer a stunning glimpse into the cutting-edge work being carried out by BHF scientists.

“The winning image is truly eye-catching. The chaotic mixture of different cells around the outside contrasts perfectly with a ‘through the looking glass’ moment where we see new and exquisitely detailed blood vessels forming in the centre.”

Dr Charmaine Griffiths, Chief Executive at the British Heart Foundation, was also a competition judge. She added:

“All of this year’s entries beautifully capture aspects of the heart and circulatory system, bringing to life the challenges that BHF scientists work tirelessly to solve.

“The images show how far we’ve come over 60 years of BHF research, and would have been barely imaginable to our founders. I love the winning image not just because of its circular beauty, but also because of the hope it represents for the future of healing damaged hearts.”

The beating heart of Royal Fort Garden

Posted on by Rachel Skerry

Bristol Heart Institute interpretation sign

The new interpretation sign for the University of Bristol brings a whole new meaning to the phrase ‘living statue’.

The solid oak monolith is the third instalment in a series of iconic totems dedicated to the University’s research institutes. This sign embodies the work of the Bristol Heart Institute and has been designed to reflect the relationship between human life and nature. Joining many other works of art in the Royal Fort Garden this piece stands proud at three metres high, and if you get close enough you can hear the low thud of a heartbeat coming from deep within the structure day and night.

Previous designs highlighted the work of the Bristol Population Health and the Bristol Bio Design Institutes.

The new monolith is built from four solid oak panels which have been laser cut and hand painted to represent a human cardiovascular system. Following a couple of years of pandemic enforced hiatus, it’s great to add to the collection and celebrate the work of the Bristol Heart Institute in such a creative way.  

(Photo by Green Hat. Words adapted from text supplied by Green Hat)

Mechanisms of cardiovascular complications in COVID-19

Posted on by Rachel Skerry

Paolo Madeddu discusses the progress of a timely research project.

Q: Why is this research significant?    

The coronavirus that causes COVID-19 enters the body through the epithelial-endothelial barrier of the lung and then spreads systemically. Its most severe manifestation is severe acute respiratory syndrome, where the epithelial-endothelial barrier is damaged to a level that fluid escapes into the alveoli. This makes it difficult for the lung to expand and allow the physiological exchanges of gases, resulting in severe hypoxia, shock and systemic organ damage. Organ damage is also caused by the virus’ ability to bring about a systemic inflammatory response and evade the immune system’s defences.

Pericytes – cells surrounding the vasculature – are essential to maintain vascular stability. We think that they can be damaged by the virus, which contributes to pulmonary and systemic damage.  We also think that the damage starts very early, when the viral S protein engages with the entry receptors expressed on cells. This is sufficient to activate detrimental signals in the pericytes and eventually prepare the ground for the virus to spread.

Q: What do you aim to do?

Our research aims to determine which receptors are expressed by human cardiac pericytes (ACE2 and also CD147, which is a more controversial receptor); determine if the S protein alone can induce signalling in exposed pericytes in culture; understand the functional consequences; and verify whether we can shield pericytes by blocking the interaction between S protein and receptors.

Q: How are you progressing?

The data we have gathered confirm the entry  receptor CD147 is expressed in pericytes. However, the expression of ACE2 receptors was low.

The S protein induces the phosphorylation of ERK1/2. This is a kinase enzyme involved in various cellular functions, but also used by the virus to activate RNA polymerase (the enzyme that makes copies of RNA and is used by the virus to make copies of itself). This reaction makes the pericytes less able to support the vascular network and also induces them to secrete inflammatory molecules typical of the cytokine storm. The instability is more evident in adult cells compared with young cells.

We can inhibit these reactions with an antibody  directed to the CD147 receptor, which suggests this is a viable method to shield human pericytes.

Our pre-prints in BioRXiv and the Lancet have received a lot of attention to date.

Q: What’s next?

Because cardiovascular patients are more  susceptible to complications from COVID-19, we  want to integrate the shielding approach of vascular cells within a more general strategy to protect the human body at the early stages of the disease.

A BHF grant is funding our work for one year. This work is carried out by Dr Elisa Avolio on cardiac pericytes provided by Professor Massimo Caputo, both acting as co-PIs.

As part of Bristol’s collective research effort into  COVID-19, we are seeking an additional  contribution from other charities and funding  agencies to work with fellow Bristol researchers  to generate an aerosol containing blockers of  entrance and attachment receptors.

This post first appeared in the March 2021 BHI Newsletter

BHF PhD programme funding renewed

Posted on by Rachel Skerry

BHI Deputy Director Alastair Poole explains the impact for our PhD in Integrative Cardiovascular Sciences.

In December 2020, the British Heart Foundation (BHF) announced new funding for its flagship four-year PhD programmes at 12 universities, aimed at nurturing the next generation of cardiovascular research leaders.

At the University of Bristol, we have been running the popular PhD programme in Integrative Cardiovascular Sciences since 2017, with tuition fees and research costs fully-funded by the BHF.

Understanding the biology and medicine of the cardiovascular system now requires approaches that cross-bridge disciplines, with our current cohort of students working across fundamental bioscience, clinical science and population health.

In this renewal, we aim to build on this successful strategy, introducing new disciplinary strands, supervisors and training in digital health, data analytics, coding and bioengineering. This aligns to the BHF strategy in aiming to prevent disease, identify and manage risk factors, through large scale genomics, data science, AI and multiparameter monitoring of environmental and medical measurements using novel personal and environmental devices. Bioengineering is now seen as an important component of regenerative medicine, and capitalizing on our broad base of expertise in Bristol, we have incorporated several new supervisors into this element. These will provide additional depth and breadth to the training for our students and further opportunities for innovative cardiovascular discovery.

When the funding was announced, Professor Metin Avkiran, the BHF’s Associate Medical Director, said:

“Today’s PhD students are tomorrow’s leaders in cardiovascular research. At this difficult time, it is more important than ever to maintain that pipeline of scientific talent and discovery towards future advances in the prevention, detection and treatment of heart and circulatory diseases.”

We look forward to welcoming our newest BHF PhD students in 2021.

PhD student Ffion Jones talks about what she enjoys about the programme:

This post first appeared in the March 2021 BHI Newsletter

The future may be on hold, but it has not been cancelled

Posted on by Rachel Skerry

BHI Director Gianni Angelini reflects on a turbulent year.

The COVID-19 pandemic made 2020 a year like no other.

It caused major disruption to our  cardiovascular research and teaching, which is continuing into 2021. Clinical translation research has virtually stopped, and basic science work has been significantly curtailed by the limited access to laboratories.

Charities, which are the backbone funders of our work, are experiencing unprecedented difficulties and this translates to reduced grant awards.  However, the renewal award of our BHF-funded PhD programme in Integrative Cardiovasular Science is excellent news.

And, at the same time, the use of  virtual platforms has transformed our work and opened avenues which were unthinkable a year ago. So, despite the gloom and doom, the pandemic is giving us a unique opportunity to regroup and reflect on what we did in the past, and what we can do better in the future.

These are the things that have not changed:

  • Our determination to continue to stand out as the leading academic cardiovascular centre in the UK, and amongst the foremost worldwide.
  • Our ability to turn innovations into benefit for adult and paediatric patients, and the health system.
  • Our creation of an environment where  clinicians, basic scientists and clinical research  methodologists can thrive, attract the most talented individuals and produce world-leading research.
  • Our resolve to facilitate a smooth and timely transition to the next generation of  cardiovascular clinicians and researchers.

This last point is possibly the most relevant for somebody heading towards the twilight of his career! We have an obligation to nurture and mentor our future research leaders by encouraging them to build the confidence to lead. We must pay more attention to our early- and mid-career  researchers and encourage them to play a  major role at the heart of our activities. They are the next generation who will guarantee our  continued success.

The future is still there for you to grab: it has not been cancelled.

This post first appeared in the March 2021 BHI Newsletter

Bristol Heart Institute (BHI) is a Specialist Research Institute at the University of Bristol.