George Abraham’s research on the role of the peptide endothelin-1 in coronary microvascular dysfunction has won the Young Investigator Award in Coronary Pathophysiology and Microcirculation at the 2023 European Society of Cardiology (ESC) Congress. UK-based researcher’s project: Transmyocardial extraction reduces endothelin-1 in cardiac allograft vasculopathy;¹ We investigated the disease pathway of cardiac allograft vasculopathy (CAV), one of the main causes of graft failure in heart transplant patients (Figure 1).

Figure 1

(L-R) Professor John McMurray, George Abraham and ESC President Franz Weidinger pictured at the 2023 ESC Conference

Dr. Abraham, BM BCh, attended Norwich School in Norfolk, England, and then went on to medical school at Oxford University. At Oxford University, cardiology stood out as an area of ​​interest. I went home and was dealt with by one team,” he says. “What also had a big impact on me was that the treatment was often dramatic. Patients come into the hospital after cardiac arrest, go to the catheterization lab, undergo procedures, and then some time later are reunited with their families. I’m sitting and drinking tea.” ” This fascination led him to join the cardiology training program at the Dean of the East of England, where he has been since 2019.

His research career began serendipitously in 2020 when he was offered a fellowship at the University of Cambridge, overseen by interventional cardiologist Dr Stephen Fuhr and cardiovascular pharmacology expert Professor Anthony Davenport. They were looking for a researcher to study coronary microvascular dysfunction and the effects of a peptide known as endothelin-1 (ET-1). ET-1 has numerous biological actions and is characterized as a highly potent vasoconstrictor. This project seemed like a good fit. “Physiology and how the body’s systems are regulated to maintain a steady state despite the extreme stress of life was one of my biggest interests in medical school. , I was happy to take up the field again in a research role.” Dr. Abraham left the training program to undertake a fellowship in 2020, much of which was dominated by the COVID-19 pandemic. However, they found new ways of working in terms of collaboration and research.

The winning work presented at the ESC meeting was a mechanistic study that investigated the role of the endothelin pathway in the progression of CAV, one of the major life-limiting diseases affecting heart transplant patients. He said: “We measured the levels of ET-1 peptide in the plasma of the coronary arteries and coronary sinus and found a significant relationship between the extent of disease and the release pattern of ET-1 peptide, defined using intracoronary imaging. We were very interested in knowing whether there is a rationale for testing endothelin receptor antagonists as a new treatment for this unique patient group. I had it.”

In addition to the award-winning research, other studies have investigated ET-1 in microvascular angina, obstructive coronary artery disease, and complications of COVID-19. “The main focus of my MD is the study of genetic mutations that affect the ET-1 pathway, which may be associated with the risk of microvascular angina, and therefore This opens up possibilities for future treatments.”

Winning the YIA award was not only a “huge honor” but also a great experience as it provided the opportunity to speak at the ESC conference. “After working online and virtually for a period of time, being able to attend a large conference and get feedback and answer questions from experts and colleagues was invaluable and led to research I hadn’t thought of. On a personal level, this award is always a big highlight in my career, but my group was also very excited about this award. Despite its history and tradition, it may not be as well-known as other institutions in clinical cardiology.

Dr. Abraham’s short-term future plans include completing his MD thesis. He recently returned to his full-time clinical training after devoting his three years to research. In the future, he would like to take up a consultant position specializing in coronary interventions that would provide protected research time to allow him to develop larger ideas (Figure 2).

Figure 2

Dr Abraham and his clinical team from the Coronary Care Unit at Addenbrookes Hospital, Cambridge, UK

His advice to aspiring researchers is to find an area you’re passionate about. Balancing clinical work and research can be a daunting task if you’re not into this subject, so it’s worth waiting for the right project. “This was my experience, but my career path was a bit unique in that I never attended an academic training program. I focused purely on clinical work until an opportunity came along in an area that really interested me. It is also important to strive to maintain a balance between work, life, and family. As the father of his two young children, Dr. Abraham understands the demands that a career in clinical research places on people’s lives. He suggests that this is also a good reason to find something you really want to work on, but he advises, “Always find time for family and non-medical interests.”

Supervisor Stephen Hall commented: “Our research group has been interested in coronary microvascular disease (CMD) and the role of ET-1, a potent vasoconstrictor, for some time. studied ET-1 in atherosclerotic cardiovascular disease, where the incidence is nearly 50%. This may explain why angina can occur even in patients without angiographic evidence of coronary artery disease. New specific treatments for CMD are urgently needed and ET -1 antagonists are potential candidates that may help improve patient symptoms, quality of life, and in some cases prognosis. We have evaluated the transmyocardial gradient (difference between coronary sinus and coronary artery plasma levels) of ET-1 and found an association.We also found that ET-1 is an important prognostic marker for patients infected with COVID-19. , microvascular dysfunction in the heart and lungs was also observed, contributing to the severity of symptoms.

“CAV is the main cause of heart failure in heart transplant patients, and CMD is thought to be important here as well. Therefore, this is important to study ET-1 expression to justify the use of ET-1 antagonists.” There was no obvious pathological condition in order to improve the function of the transplanted heart.

“Heart transplantation is a rare and valuable resource, and it is important to prevent CAV and thereby prolong cardiac transplant function in patients. We found that the transmyocardial gradient of ET-1 was higher in coronary arteries with CAV, which suggests that ET-1 is probably secreted from the affected coronary artery wall, which may be responsible for accelerating progression. of CAV. Our data suggest the use of ET-1 antagonists as a disease-modifying therapy for CAV that may reduce CAV-associated comorbidities and prolong transplanted heart function. A pilot is warranted. This initial study provides an important legacy for ongoing research.”

“George was essential to the analysis, interpretation, and presentation of this work. In particular, he quickly understood the project, demonstrated scientific rigor in data analysis and interpretation, and the ability to explain results clearly and concisely. It was a pleasure to supervise him, and I hope he continues to work in academic cardiology after he completes his Ph.D.

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Disclosure of interests

All authors declare that they do not disclose any interest in this contribution.

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