title: An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF)-α is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-α antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model.
  
  
  METHODS
  Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-α, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)2, and tissue inhibitor of matrix metalloproteinase (TIMP).
  
  
  RESULTS
  The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intra-acinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-α, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28).
  
  
  CONCLUSIONS
  Infliximab administration induced early changes in pathological findings and expression levels of TNF-α, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.
authors.affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kwon
authors.forename: Kwan Chang
authors.initials: KC
authors.lastname: Kim
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Cho
authors.forename: Hae Soon
authors.initials: HS
authors.lastname: Kim
authors.forename: Sejung
authors.initials: S
authors.lastname: Sohn
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Hong
keywords: Gene expression; Infliximab; Monocrotaline; Pulmonary hypertension
references.citation: Am J Respir Crit Care Med. 2004 Jan 1;169(1):39-45
references.pmid: 12958054
references.citation: Korean Circ J. 2010 Sep;40(9):459-64
references.pmid: 20967148
references.citation: J Mol Cell Cardiol. 2000 Jan;32(1):109-20
references.pmid: 10652195
references.citation: Arthritis Res Ther. 2007;9 Suppl 2:S8
references.pmid: 17767746
references.citation: J Mol Med (Berl). 2011 Aug;89(8):771-83
references.pmid: 21809123
references.citation: Nat Med. 2000 Jun;6(6):698-702
references.pmid: 10835689
references.citation: J Appl Physiol (1985). 1991 Dec;71(6):2483-92
references.pmid: 1838107
references.citation: J Clin Invest. 2005 Jun;115(6):1479-91
references.pmid: 15931388
references.citation: FASEB J. 2005 Jul;19(9):1178-80
references.pmid: 15897232
references.citation: Circulation. 2004 Apr 13;109(14):1718-23
references.pmid: 15037536
references.citation: Korean Circ J. 2011 Sep;41(9):518-27
references.pmid: 22022327
references.citation: Pediatr Res. 2001 Aug;50(2):172-83
references.pmid: 11477200
references.citation: J Immunol. 2009 Aug 15;183(4):2741-6
references.pmid: 19620291
references.citation: Korean Circ J. 2011 Feb;41(2):83-90
references.pmid: 21430993
references.citation: J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):13S-24S
references.pmid: 15194174
references.citation: Circ Res. 1993 Nov;73(5):887-97
references.pmid: 8403258
references.citation: Gut. 2002 Feb;50(2):206-11
references.pmid: 11788561
references.citation: Am J Respir Crit Care Med. 2004 Jan 1;169(1):34-8
references.pmid: 14525801
references.citation: J Pharmacol Exp Ther. 1997 Sep;282(3):1312-8
references.pmid: 9316840
references.citation: Circulation. 2004 Jan 20;109(2):159-65
references.pmid: 14734504
references.citation: J Rheumatol. 1997 Apr;24(4):663-5
references.pmid: 9101498
references.citation: Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1497-505
references.pmid: 15923311
references.citation: Lung. 1999;177(2):77-88
references.pmid: 9929405
references.citation: Respiration. 2008;75(3):346-9
references.pmid: 16369127
references.citation: Pediatr Res. 2006 Sep;60(3):245-51
references.pmid: 16857764
references.citation: Respir Res. 2009 Nov 13;10:110
references.pmid: 19912632
references.citation: Genes Dev. 2000 Sep 1;14(17):2123-33
references.pmid: 10970876
references.citation: Pediatr Crit Care Med. 2010 Mar;11(2 Suppl):S10-4
references.pmid: 20216155
references.citation: Eur Respir J. 2003 Aug;22(2):358-63
references.pmid: 12952274
references.citation: Cardiovasc Res. 2002 Mar;53(4):822-30
references.pmid: 11922892
references.citation: Circulation. 2003 Jul 1;107(25):3133-40
references.pmid: 12796126