CD73 on Immune Cells Protects from Adverse Cardiac Remodeling

Rationale: CD73 (ecto-59-nucleotidase) on immune cells is emerging as critical pathway and therapeutic target in cardiovascular and autoimmune disorders. Objective: Here we investigated the role of CD73 in post infarction inflammation, cardiac repair and remodelling in mice after reperfused myocardial infarction (50 min ischemia). Methods and Results: We found that compared to control mice a) cardiac function in CD73 -/- mice more severely declined after infarction (systolic failure with enhanced myocardial oedema formation) as determined by MRI and was associated with the persistence of cardiac immune cell subsets, b) cardiac adenosine release was augmented 7 days after I/R in control mice but reduced by 90% in CD73 mutants, c) impaired healing involves M1-driven immune response with increased TNF-α and IL-17 as well as decreased TGF-β and IL-10, d) CD73 -/- mice displayed infarct expansion accompanied by an immature replacement scar and diffuse ventricular fibrosis. Studies on mice after bone marrow transplantation revealed that CD73 present on immune cells is a major determinant promoting cardiac healing. Conclusions: These results together with the upregulation of CD73 on immune cells after I/R demonstrate the crucial role of purinergic signaling during cardiac healing and provide groundwork for novel anti-inflammatory strategies in treating adverse cardiac remodeling.