title: Angiotensin 1-7 significantly reduces diabetes-induced leukocyte recruitment both in vivo and in vitro.
abstract: OBJECTIVE
  Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment.
  
  
  METHODS
  Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion.
  
  
  RESULTS
  Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects.
  
  
  CONCLUSIONS
  Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro. These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis.
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy. Electronic address: fbossi@units.it.
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Bernardi
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: De Nardo
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bramante
authors.affiliation: Centro Diabetologico ASS 1 Triestina, Via Puccini, 34100 Trieste, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Candido
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Carretta
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fischetti
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34100 Trieste, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fabris
mesh_terms: D000803:Angiotensin I; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments; D012313:RNA / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015815:Cell Adhesion Molecules; D010446:Peptide Fragments; D012313:RNA; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Angiotensin; Diabetes; Intravital microscopy; Leukocyte-endothelial adhesion; Renin-angiotensin system