The role of eosinophils (EOS) in cardiovascular disease (CVD) has been primarily investigated through clinical associations, with recent preclinical studies suggesting a potential causal involvement. However, conflicting observations in clinical studies and limitations in experimental disease models have left unanswered questions. It is crucial to consider data collection methods and disease nature, as information from early time-points and acute events may differ from community or chronic disease studies.
Clinical observations reveal contradictory findings regarding the association between elevated and reduced blood EOS count and eosinophil cationic protein (ECP) levels, indicating a dual role in the higher risk of myocardial infarction (MI). Preclinical studies demonstrate that EOS exert cardioprotective actions in MI by releasing interleukin-4 and ECP, preventing cardiac cell death and fibrosis. However, EOS also express proteins that contribute to atherosclerosis, thrombosis, and associated complications, suggesting diverse roles in different stages of cardiovascular disease.
Our research focuses on exploring the association of EOS with cardiovascular outcomes or risk factors in different stages of MI. We aim to compare the clinical prognostic value of blood EOS count and percentage in various stages of MI for predicting major adverse cardiovascular endpoints (MACE). Additionally, we plan to evaluate causal relationships for clinical outcomes using human genetics and related risk factors through a Mendelian randomization approach.
Through this proposed research, we anticipate gaining a better understanding of EOS and its role in the risk of cardiovascular events within different MI sub-populations of the UK Biobank. We aim to elucidate how EOS causally relates to the risk of cardiovascular events, providing insights to improve treatment strategies for individuals recovering from cardiovascular disease. Subsequently, this approach may be extended to other cardiovascular diseases. The full cohort and estimated duration of the project are three years.