title: Ecto-5'-nucleotidase on immune cells protects from adverse cardiac remodeling.
abstract: BACKGROUND
  Ecto-5'-nucleotidase (CD73) on immune cells is emerging as a critical pathway and therapeutic target in cardiovascular and autoimmune disorders.
  
  
  OBJECTIVE
  Here, we investigated the role of CD73 in postinfarction inflammation, cardiac repair, and remodeling in mice after reperfused myocardial infarction (50-minute ischemia).
  
  
  RESULTS
  We found that compared with control mice (1) cardiac function in CD73(-/-) mice more severely declined after infarction (systolic failure with enhanced myocardial edema formation) as determined by MRI and was associated with the persistence of cardiac immune cell subsets, (2) cardiac adenosine release was augmented 7 days after ischemia/reperfusion in control mice but reduced by 90% in CD73 mutants, (3) impaired healing involves M1-driven immune response with increased tumor necrosis factor-α and interleukin-17, as well as decreased transforming growth factor-β and interleukin-10, and (4) 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 ischemia/reperfusion, demonstrate the crucial role of purinergic signaling during cardiac healing and provide groundwork for novel anti-inflammatory strategies in treating adverse cardiac remodeling.
authors.affiliation: Department of Molecular Cardiology, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bönner
authors.forename: Nadine
authors.initials: N
authors.lastname: Borg
authors.forename: Christoph
authors.initials: C
authors.lastname: Jacoby
authors.forename: Sebastian
authors.initials: S
authors.lastname: Temme
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Ding
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flögel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schrader
mesh_terms: D015720:5'-Nucleotidase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D007111:Immunity, Cellular / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015720:5'-Nucleotidase
keywords: CD73; adenosine; inflammation; myocardial infarction