Proteomics in Action: Finding the Right Drug Targets for Ischemic Heart Disease | JACC Baran

Which of the thousands of biomarkers associated with cardiovascular disease could actually become a useful drug target? Host Mitsuaki Sawano, MD, and co-host Nobuhiro Ikemura, MD, welcome Satoshi Yoshiji, MD, PhD (McGill University) to discuss a recent JACC study tackling this question in ischemic heart disease. Starting with 9,520 circulating proteins, the investigators used human genetics to move beyond association toward stronger evidence for causality, combining Mendelian randomization, genetic colocalization, multiple proteomic platforms, and cross-ancestry validation to narrow thousands of signals to a small group of potential therapeutic targets. We break down what these methods actually mean for clinicians: what cis-pQTLs tell us, why MR alone is not enough, what colocalization adds, and why validation across platforms and populations matters. The episode explores how this emerging approach could help determine which biological targets are worth pursuing in drug development and ultimately testing in clinical trials.