Targeting B cells of the pericardium to improve outcome post-myocardial infarction

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Heart attack is the cause of as many as 100,000 hospital admissions each year in the UK. While most people survive, the injury results in loss of heart muscle and scarring putting patients at increased risk of chronic heart failure. After a heart attack, the body mounts an inflammatory response to clear dying tissue and repair the damage to the heart. This is a very important process as it determines how well the heart will heal and the patients risk of developing heart failure. Therapeutic strategies targeting specific aspects of the inflammatory response after a heart attack may prove particularly effective to improve heart repair and reduce risk of developing chronic heart failure. The heart is enveloped by a protective sac called the pericardium. We have discovered that the outer-layer of the pericardium, also called parietal pericardium, has important immunologic properties. In particular, it contains a type of white blood cell called B cells, well known for their role in the production of antibodies during infection and after vaccination. Pre-clinical models have now shown that B cells of the parietal pericardium can control the immune cell response triggered by a heart attack and help repair the heart. Thus, targeting these B cells to boost their protective properties post-heart attack to improve cardiac outcome has clear clinical translation. To develop such treatments, we need to better understand the B cells of the parietal pericardium in humans.In this project, we will work with surgeons performing heart operations to obtain fat samples from the pericardium from consenting patients. We will work out exactly how human pericardial B cells are activated after heart attack and identify the key proteins that control their protective function. We also want to identify the molecules that activates these B cells so that we can target them. This could be done using liposomes or lipid nanoparticles resembling those used to deliver COVID-19 mRNA vaccine. We will test whether specific substances added to liposomes can activate pericardial B cells and boost their protective function. Using a pre-clinical model of heart attack, we will test if these substances can improve healing of the heart and preserves its function after heart attack. We believe that this work will lead to the development of a new way of treating heart attack.