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Cell Biochemistry and Biophysics

, Volume 44, Issue 1, pp 1–9 | Cite as

DNA microarray analysis for human congenital heart disease

  • Hari S. Sharma
  • Theodorus H. F. Peters
  • Michael J. Moorhouse
  • Peter J. van der Spek
  • Ad J. J. C. Bogers
Review

Abstract

Right ventricular hypertrophy and failure are prominent features in cyanotic congenital heart disease, tetralogy of Fallot (TF). Patients with TF require primary cardiac surgery at a very young age. To gain insight into the underlying molecular mechanisms of right ventricular hypertrophy and to identify gene(s) involved in TF, differential gene expression profile was assessed using expression-based microarray technology on right ventricular biopsies from young TF patients who underwent primary correction. By using quantitative immunohistochemistry, expression of vascular endothelial growth factor (VEGF), flk-1, and extracellular matrix (ECM) proteins (collagens and fibronectin) as well as vessel counts and myocyte cell size was evaluated in TF patients in relation to age-matched controls. Among 236 genes showing altered expression pattern in TF patients, VEGF (1.8-fold) and ECM markers were clearly upregulated (fibronectin, 2.4-fold; collagen Iα, 7.5-fold; and collagen III, 4.4-fold); flk-1 and most matrix metalloproteinases (MMPs) remained unchanged, except the levels of MMP-13 and-17 declined. Tissue inhibitors of metalloproteinases showed a downregulated pattern. Staining of VEGF in cardiomyocytes and of ECM proteins (fibronectin, collagen I and III) in interstitial as well as in perivascular area was increased (p<0.01) in TF patients. Morphometric analysis revealed enhanced vascular density (p<0.05) with unchanged wall thickness and enlarged myocyte cross-sectional areas (p<0.01) with linear correlation (p<0.01) with the age in TF-1 patients. We conclude that the upregulation of genes encoding VEGF and ECM proteins are the key events contributing to right ventricular hypertrophy and stunted angiogenesis in patients with TF.

Index Entries

Tetralogy of Fallot right ventricular hypertrophy DNA microarray fibrosis angiogenesis video image analysis 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Hari S. Sharma
    • 1
  • Theodorus H. F. Peters
    • 1
    • 2
  • Michael J. Moorhouse
    • 3
  • Peter J. van der Spek
    • 3
  • Ad J. J. C. Bogers
    • 2
  1. 1.Department of PharmacologyUniversity Medical CenterRotterdamThe Netherlands
  2. 2.Department of Cardiothoracic SurgeryUniversity Medical CenterRotterdamThe Netherlands
  3. 3.Department of Bioinformatics, Erasmus MCUniversity Medical CenterRotterdamThe Netherlands

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