title: Interleukin-2 enhances angiogenesis and preserves cardiac function following myocardial infarction.
abstract: We previously demonstrated that injection of IL-2-activated natural killer (NK) cells contribute to vascular remodeling via a4b7 integrin and killer cell lectin-like receptor (KLRG) 1 and promote cardiac repair following myocardial infarction (MI). The aim of the present study is to test the hypothesis that injection of recombinant human interleukin (rhIL)-2 improves angiogenesis and preserves heart function after MI. A single IV injection of rhIL-2 two days following MI improved by 27.7% the left ventricular (LV) fractional shortening of immune competent (C57Bl6) mice, but had no effect on cardiac function of immune-deficient (NOD-SCID IL2Rγnull) mice. Immunohistochemical analysis of C57Bl6 cross sections of heart revealed that collagen deposition was reduced by 23.1% and that capillary density was enhanced in the scar area and the border zone of the infarct respectively by 22.4% and 33.6% following rhIL-2 injection. In addition, rhIL-2 enhanced 1.6-fold the in vivo endothelial cell proliferation index and 1.8-fold the number of NK cell infiltrating the infarcted heart, but had no effect on the number of cardiac CD4 and CD8 cells. In vitro, rhIL-2 activated NK cells enhanced cardiac endothelial cell proliferation by 17.2%. Here we show that a single IV injection of rhIL-2 positively impacted cardiac function by improving angiogenesis through a process involving NK cells.
authors: Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, 3755 Cote Ste-Catherine Road, Montreal, Quebec, Canada H3T 1E2.
authors: M
authors: M
authors: Bouchentouf
authors: P
authors: P
authors: Williams
authors: K A
authors: KA
authors: Forner
authors: J
authors: J
authors: Cuerquis
authors: V
authors: V
authors: Michaud
authors: P
authors: P
authors: Paradis
authors: E L
authors: EL
authors: Schiffrin
authors: J
authors: J
authors: Galipeau
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006321:Heart / Q000503:physiopathology*; D006334:Heart Function Tests / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D007376:Interleukin-2; D003094:Collagen