Multiomic Spatial Mapping of Myocardial Infarction and Implications for Personalized Therapy

Abstract

Ischemic heart disease including myocardial infarction is still the leading cause of death worldwide. Although the survival early after myocardial infarction has been significantly improved by the introduction of percutaneous coronary intervention, long-term morbidity and mortality remain high. The elevated long-term mortality is mainly driven by cardiac remodeling processes triggering ischemic heart failure and electric instability. Despite the new developments in pharmaco-therapy of heart failure, we still lack targeted therapies for cardiac remodeling and fibrosis. Single-cell and genomic technologies allow us to map the human heart at unprecedented resolution and allow to gain insights into cellular and molecular heterogeneity. However, these technologies rely on digested tissue and isolated cells or nuclei and thus lack spatial information. Spatial information is critical to understand tissue homeostasis and disease and can be utilized to identify disease-driving cell populations and mechanisms including cellular cross-talk. Here, we discuss recent advances in single-cell and spatial genomic technologies that give insights into cellular and molecular mechanisms of cardiac remodeling after injury and can be utilized to identify novel therapeutic targets and pave the way toward new therapies in heart failure.