title: Plasma proANP and SDMA and microRNAs are associated with chronic mitral regurgitation in a pig model.
abstract: OBJECTIVE
  NON-ISCHEMIC MITRAL REGURGITATION (MR) IS PRIMARILY CAUSED BY MYXOMATOUS MITRAL VALVE (MV) DISEASE LEADING TO ADAPTIVE REMODELING, ENLARGEMENT, AND DYSFUNCTION OF THE LEFT VENTRICLE. THE AIM OF THIS STUDY WAS TO EXAMINE THE REGULATION OF PLASMA MARKERS AND SEVERAL CARDIAC KEY GENES IN A NOVEL PORCINE MODEL OF NON-ISCHEMIC MR.
  
  
  RESULTS
  Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20-50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR ≤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (P<0.05). The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05).
  
  
  CONCLUSIONS
  Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model.
authors.affiliation: Department of Veterinary Clinical and Animal SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark Novo Nordisk A/SMaaloev, Denmark Department of Clinical BiochemistryCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Department of Cardiothoracic and Vascular SurgeryAarhus University Hospital, Aarhus, Denmark Department of Clinical BiochemistryAarhus University Hospital, Aarhus, Denmark Department of Veterinary Disease BiologyFaculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark Department of Clinical ChemistryVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cirera
authors.forename: Sophia G
authors.initials: SG
authors.lastname: Moesgaard
authors.forename: Nora E
authors.initials: NE
authors.lastname: Zois
authors.forename: Nathja
authors.initials: N
authors.lastname: Ravn
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.forename: Signe E
authors.initials: SE
authors.lastname: Cremer
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Páll S
authors.initials: PS
authors.lastname: Leifsson
authors.forename: Jesper L
authors.initials: JL
authors.lastname: Honge
authors.forename: J Michael
authors.initials: JM
authors.lastname: Hasenkam
authors.forename: Lisbeth H
authors.initials: LH
authors.lastname: Olsen
keywords: SDMA; microRNA; mitral regurgitation; pig; proANP
references.citation: Cardiovasc Pathol. 2006 Jul-Aug;15(4):185-93
references.pmid: 16844549
references.citation: J Heart Valve Dis. 2012 May;21(3):299-310
references.pmid: 22808829
references.citation: Eur Heart J. 1996 Dec;17(12):1875-81
references.pmid: 8960431
references.citation: Am J Vet Res. 2011 Feb;72(2):194-202
references.pmid: 21281193
references.citation: J Vet Med A Physiol Pathol Clin Med. 2007 Apr;54(3):156-60
references.pmid: 17381681
references.citation: Minn Med. 1976 Sep;59(9):637-47
references.pmid: 967136
references.citation: Adv Vet Sci Comp Med. 1977;21:75-106
references.pmid: 146409
references.citation: Circ Res. 2010 Jan 8;106(1):16-8
references.pmid: 20056941
references.citation: J Heart Valve Dis. 2008 May;17(3):283-9
references.pmid: 18592925
references.citation: J Comp Pathol. 2008 Aug-Oct;139(2-3):97-107
references.pmid: 18640684
references.citation: Atherosclerosis. 2010 Oct;212(2):512-5
references.pmid: 20655043
references.citation: J Vet Cardiol. 2012 Mar;14(1):59-71
references.pmid: 22364722
references.citation: Clin Chem. 2011 Jan;57(1):112-21
references.pmid: 21036946
references.citation: J Vet Intern Med. 2012 Jan-Feb;26(1):61-8
references.pmid: 22151409
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18255-60
references.pmid: 17108080
references.citation: Anal Biochem. 2002 Apr 15;303(2):131-7
references.pmid: 11950212
references.citation: J Vet Cardiol. 2012 Sep;14(3):399-408
references.pmid: 22858663
references.citation: Vet J. 2009 May;180(2):195-201
references.pmid: 18675567
references.citation: BMC Mol Biol. 2007 Aug 15;8:67
references.pmid: 17697375
references.citation: Front Biosci (Landmark Ed). 2012 Jan 01;17:1804-15
references.pmid: 22201837
references.citation: Anal Biochem. 2006 Jun 15;353(2):287-9
references.pmid: 16603118
references.citation: Circ Res. 2010 Jan 8;106(1):166-75
references.pmid: 19893015
references.citation: Life Sci. 2006 Apr 25;78(22):2633-42
references.pmid: 16310223
references.citation: BMC Biotechnol. 2011 Jun 25;11:70
references.pmid: 21702990
references.citation: Nephrol Dial Transplant. 2006 Sep;21(9):2446-51
references.pmid: 16766542
references.citation: J Mol Cell Cardiol. 2011 Oct;51(4):600-6
references.pmid: 21059352
references.citation: Nat Med. 2007 May;13(5):613-8
references.pmid: 17468766
references.citation: Vet J. 2009 Apr;180(1):88-94
references.pmid: 18295518
references.citation: Cardiovasc Res. 2000 Aug;47(2):234-43
references.pmid: 10946060
references.citation: J Heart Valve Dis. 2012 Jul;21(4):416-23
references.pmid: 22953665
references.citation: Am J Pathol. 2007 Jun;170(6):1831-40
references.pmid: 17525252
references.citation: J Comp Pathol. 2009 May;140(4):271-7
references.pmid: 19285315
references.citation: N Engl J Med. 1998 Jul 30;339(5):321-8
references.pmid: 9682046
references.citation: J Immunol Methods. 2011 Jul 29;370(1-2):104-10
references.pmid: 21703274