title: Progression of matrixin and cardiokine expression patterns in an ovine model of heart failure and recovery.
abstract: BACKGROUND
  The molecular mechanisms underlying the geometrical changes of the left ventricle during the progression to heart failure and recovery are not well defined.
  
  
  OBJECTIVE
  Here we investigate the involvement of matrixins and cardiokines in an ovine model of pressure-induced left ventricular failure (LVF).
  
  
  METHODS
  Fifteen sheep underwent supracoronary aortic banding with an inflatable cuff. A controlled and progressive increase of LV pressure was monitored echocardiographically. Endomyocardial biopsies were collected throughout the development of LVF and subsequent recovery after pressure unloading.
  
  
  RESULTS
  Thirteen sheep developed LVF with a subsequent recovery. Peak left ventricular hypertrophy (LVH) and dilatation (LVD) occurred at 31.5 ± 1.6 weeks and 102.7 ± 2.2 weeks post-banding respectively, with an increase in LV internal diameter in diastole (LVIDd 5.11 ± 0.12 compared to the control 3.37 ± 0.07 cm, p<0.001), with preserved LV ejection fraction (LVEF). Reduced LVEF became evident 116.5 ± 2.7 weeks post-banding. Clinical and echocardiographic improvements were observed following deflation of the aortic banding cuff. By 138.1 ± 3.1 weeks cardiac performance recovered with restoration of LVEF. Significant changes in the expression of matrix metalloproteinases (MMP)-1, -2, -3, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF)-2, interferon (INF)-α-2 and soluble CD40 ligand (sCD40L) were observed throughout the progression to failure and recovery.
  
  
  CONCLUSIONS
  We used an ovine model to study reversible LV remodelling without interruption and found significant changes in matrixin and cardiokine expression during LV progression to failure and recovery.
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Mohammed
authors: M
authors: Quttainah
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Reem
authors: R
authors: Al-Hejailan
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Soad
authors: S
authors: Saleh
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Ranjit
authors: R
authors: Parhar
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia; Department of Medicine, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia; Alfaisal University, College of Medicine, Riyadh 11533, Saudi Arabia.
authors: Walter
authors: W
authors: Conca
authors: Non-invasive Cardiovascular Research, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Bernard
authors: B
authors: Bulwer
authors: Department of Cardiothoracic Surgery, Papworth Hospital, University of Cambridge, Cambridge CB23 3RE, UK.
authors: Narain
authors: N
authors: Moorjani
authors: Department of Cardiothoracic Surgery, Papworth Hospital, University of Cambridge, Cambridge CB23 3RE, UK.
authors: Pedro
authors: P
authors: Catarino
authors: Department of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia.
authors: Raafat
authors: R
authors: Elsayed
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Mohammed
authors: M
authors: Shoukri
authors: King Faisal Heart Centre, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Mansour
authors: M
authors: AlJufan
authors: King Faisal Heart Centre, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Maie
authors: M
authors: AlShahid
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia; Alfaisal University, College of Medicine, Riyadh 11533, Saudi Arabia.
authors: Abderrahman
authors: A
authors: Ouban
authors: King Faisal Heart Centre, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Zohair
authors: Z
authors: Al-Halees
authors: Oxford Heart Centre, John Radcliffe Hospital, Oxford 0X9 3DU, UK.
authors: Stephen
authors: S
authors: Westaby
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia.
authors: Kate
authors: K
authors: Collison
authors: Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, 11211 Riyadh, Saudi Arabia; Alfaisal University, College of Medicine, Riyadh 11533, Saudi Arabia. Electronic address: futwan@kfshrc.edu.sa.
authors: Futwan
authors: F
authors: Al-Mohanna
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015151:Immunoblotting; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000502:physiology*; D012756:Sheep; D034561:Sheep, Domestic; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D012313:RNA; D020782:Matrix Metalloproteinases
keywords: Aortic banding; Cardiokines; Matrixins; Pressure overload