title: The effect of impaired angiogenesis on intestinal function following massive small bowel resection.
abstract: OBJECTIVE
  Intestinal adaptation involves villus lengthening, crypt deepening, and increased capillary density following small bowel resection (SBR). Mice lacking the proangiogenic chemokine CXCL5 have normal structural adaptation but impaired angiogenesis. This work evaluates the impact of incomplete adaptive angiogenesis on the functional capacity of the intestine after SBR.
  
  
  METHODS
  CXCL5 knockout (KO) and C57BL/6 wild-type (WT) mice underwent 50% SBR. Magnetic resonance imaging measured weekly body composition. Intestinal absorptive capacity was evaluated through fecal fat analysis. Gene expression profiles for select macronutrient transporters were measured via RT-PCR. Postoperative crypt and villus measurements were assessed for structural adaptation. Submucosal capillary density was measured through CD31 immunohistochemistry.
  
  
  RESULTS
  Comparable postoperative weight gain occurred initially. Diminished weight gain, impaired fat absorption, and elevated steatorrhea occurred in KO mice after instituting high-fat diet. Greater postoperative upregulation of ABCA1 fat transporter occurred in WT mice, while PEPT1 protein transporter was significantly downregulated in KO mice. KO mice had impaired angiogenesis but intact structural adaptation.
  
  
  CONCLUSIONS
  After SBR, KO mice display an inefficient intestinal absorption profile with perturbed macronutrient transporter expression, impaired fat absorption, and slower postoperative weight gain. In addition to longer villi and deeper crypts, an intact angiogenic response may be required to achieve functional adaptation to SBR.
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Jose
authors.initials: J
authors.lastname: Diaz-Miron
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Raphael
authors.initials: R
authors.lastname: Sun
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Pamela
authors.initials: P
authors.lastname: Choi
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sommovilla
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Erwin
authors.affiliation: Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Mei
authors.affiliation: Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: G
authors.initials: G
authors.lastname: Scott Worthen
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St Louis, MO. Electronic address: brad.warner@wustl.edu.
authors.forename: Brad W
authors.initials: BW
authors.lastname: Warner
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D054365:Chemokine CXCL5; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000502:physiology / Q000601:surgery*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic
chemical_list: D054365:Chemokine CXCL5
keywords: Angiogenesis; CXCL5; Functional intestinal adaptation; High-fat diet; Small bowel resection
references.citation: Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1928-36
references.pmid: 18757292
references.citation: J Pediatr Surg. 2008 Jan;43(1):14-9
references.pmid: 18206448
references.citation: J Pediatr Surg. 2009 Jun;44(6):1077-82; discussion 1083
references.pmid: 19524720
references.citation: Surgery. 2010 Aug;148(2):364-70
references.pmid: 20471049
references.citation: Immunity. 2010 Jul 23;33(1):106-17
references.pmid: 20643340
references.citation: J Nutr. 2010 Nov;140(11):1907-14
references.pmid: 20861213
references.citation: J Pediatr Surg. 2011 Jun;46(6):1045-51
references.pmid: 21683196
references.citation: J Nutr Biochem. 2012 Jan;23(1):1-7
references.pmid: 21684139
references.citation: J Clin Invest. 2012 Mar;122(3):974-86
references.pmid: 22326959
references.citation: Curr Opin Lipidol. 2012 Jun;23(3):196-200
references.pmid: 22488425
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Jul;303(1):G93-102
references.pmid: 22538401
references.citation: J Pediatr Surg. 2014 Jun;49(6):976-80; discussion 980
references.pmid: 24888846
references.citation: J Pediatr Surg. 2008 Jun;43(6):1018-24
references.pmid: 18558176
references.citation: J Immunol. 2000 Nov 1;165(9):5269-77
references.pmid: 11046061
references.citation: J Biol Chem. 1996 Jul 26;271(30):18024-31
references.pmid: 8663430
references.citation: Cancer Metastasis Rev. 1996 Jun;15(2):149-51
references.pmid: 8842485
references.citation: J Am Coll Surg. 1996 Nov;183(5):441-9
references.pmid: 8912612
references.citation: Gastroenterology. 1997 Jul;113(1):332-40
references.pmid: 9207295
references.citation: Gastroenterology. 1997 Sep;113(3):808-16
references.pmid: 9287972
references.citation: J Biol Chem. 2005 Oct 14;280(41):34764-75
references.pmid: 16085642
references.citation: J Pediatr Surg. 2007 Jan;42(1):1-11
references.pmid: 17208533
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Sep;293(3):G591-8
references.pmid: 17585015
references.citation: J Biol Chem. 2009 Jan 2;284(1):134-40
references.pmid: 18981186