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ESC William Harvey Lecture in Basic Science: Prof. Lina Badimon

Tissue factor in the continuum of cardiovascular disease progression: effects beyond thrombosis

26 Aug 2023

The presenter of this year’s ESC William Harvey Lecture in Basic Science, Professor Lina Badimon (Cardiovascular Program-ICCC, IR-Hospital de la Santa Creu i Sant Pau, UAB, CIBERCV - Barcelona, Spain), has made significant steps in unravelling the complexity of atherosclerosis and identifying innovative disruptive strategies.

What first made you interested in CV research?

The burden of atherosclerotic CVD as the main cause of death worldwide, and the challenge it poses for patients and doctors, led me to choose cardiology as the focus of my professional life and research interest. My aim has always been to try to find prevention and treatment opportunities that will have a clinically meaningful impact. After completing my post-graduate studies in Spain, I spent 15 years in the US – at The Mayo Clinic, Mount Sinai Medical Center and then Harvard Medical School – conducting research into atherosclerosis and the myocardial injury that results from an ischaemic episode. Returning to Spain in the mid-1990s, I have continued to explore cardioprotection in the context of myocardial infarction (MI). While this is an area that has been extensively investigated by many researchers, there are still no tangible results. We have the tools to improve coronary vessel patency, but myocardial lesions, which can lead to scarring and the risk of progression to heart failure, are still not treatable.

What are the key themes of your lecture?

My lecture discusses a project I first began to work on in the US – the role of tissue factor in CVD progression. I think it is a good illustration of how basic science can be used first to understand a clinical problem and then to find a solution for that problem. Tissue factor is a key component of thrombotic events that, together with end-stage atherosclerosis, lead to MI. Taking advantage of new molecular technologies, and helped by funding from Spain’s Ministry of Health, my laboratory has successfully produced a triple mutant of tissue factor that is devoid of thrombotic activity but that retains its angiogenic capacity. We are now using this modified protein to try to get a better understanding of the effects of infarction on the myocardium. In addition, we are investigating the potential of this tissue factor mutant in the context of ischaemic damage, both as therapy – to promote regeneration of the microvasculature and therefore stimulate tissue reperfusion – and in the prevention of injury. The lecture highlights the importance of innovation in developing new drugs for prevention and treatment. We need to maximise the potential of the advanced technologies available to us to develop biological agents that will change lives.

What are the current challenges in your field?

Cardioprotection constitutes a huge unmet medical need. The main challenge is simply that there are no effective agents and this is why we continue to focus our research in this area. Our tissue factor mutant has shown promising activity in in vitro cell cultures, including 3D cultures, and in small-animal models. The next step is to demonstrate its efficacy preclinically in a porcine model. Accounting for the time taken to patent the agent and to acquire investment, we hope that the translational implications of our findings will become apparent in the next few years, when we expect to able to initiate the first clinical trials.

Where do you think research in your field is heading in the future?

There are many other initiatives underway looking at cardioprotection. One avenue of research involves investigating how to repurpose existing medicines. The biggest rewards are likely to come from the use of new technologies, both at the molecular level and in imaging, which will play an increasingly important role in advancing our understanding of cardiac disease, in identifying patients requiring early intervention and in the development of effective preventive strategies. We are currently looking at biomarkers of cardiogenic shock, which is an indicator of poor prognosis in patients with an MI. Research to date suggests that microRNAs may have a potential role in this area. We are also investigating the pathophysiology of, and biomarkers for, familial hypercholesterolaemia, which carries a high risk of premature atherosclerosis.