Ecto-5'-Nucleotidase on Immune Cells Protects From Adverse Cardiac Remodeling

F. Bonner, N. Borg, C. Jacoby, S. Temme, Z. Ding, U. Flogel, J. Schrader
2013 Circulation Research  
Rationale: CD73 (ecto-5´-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
more » ... ilure 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.
doi:10.1161/circresaha.113.300180 pmid:23720442 fatcat:7cvtjt435zd6vdrtrr7mjkwtle