title: CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice.
abstract: OBJECTIVE
  To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion.
  
  
  RESULTS
  Seven days post-permanent ligation, hearts from CD13 knockout (CD13(KO)) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13(KO) infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13(KO) mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13(KO) infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13(KO) infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling.
  
  
  CONCLUSIONS
  In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing.
authors.affiliation: Center for Vascular Biology MC3501, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3501, USA.
authors.forename: Flavia E
authors.initials: FE
authors.lastname: Pereira
authors.forename: Chunxia
authors.initials: C
authors.lastname: Cronin
authors.forename: Mallika
authors.initials: M
authors.lastname: Ghosh
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.forename: Mariela
authors.initials: M
authors.lastname: Agosto
authors.forename: Jaganathan
authors.initials: J
authors.lastname: Subramani
authors.forename: Ruibo
authors.initials: R
authors.lastname: Wang
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Shen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schacke
authors.forename: Brannen
authors.initials: B
authors.lastname: Liang
authors.forename: Tie Hong
authors.initials: TH
authors.lastname: Yang
authors.forename: Beata
authors.initials: B
authors.lastname: McAulliffe
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Liang
authors.forename: Linda H
authors.initials: LH
authors.lastname: Shapiro
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D018826:CD13 Antigens / Q000032:analysis / Q000502:physiology*; D002465:Cell Movement; D054059:Coronary Occlusion / Q000150:complications*; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology; D058628:Myofibroblasts / Q000737:chemistry; D020257:Ventricular Remodeling; D014945:Wound Healing
chemical_list: D000199:Actins; C544013:alpha-smooth muscle actin, mouse; D018826:CD13 Antigens
keywords: CD13; Dendritic cells; Macrophages; Monocytes; Myocardial infarction