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The Hypertrophied Heart pp 227–241Cite as

Angiogenesis and Fibrosis During Right Ventricular Hypertrophy in Human Tetralogy of Fallot

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 3))

Summary

Right ventricular hypertrophy (RVH) due to pressure as well as volume overload caused by (sub) pulmonary stenosis and ventricular septal defect is one of the main features in human tetralogy of Fallot (TF). Currendy, primary correction at a very young age is the treatment of choice. However, it is not yet known to what extent RVH in TF patients regresses after corrective surgery. The aim of our study was to evaluate the changes in magnitude of the myocardial fibrosis and angiogenesis during RVH in patients undergoing corrective surgery. For this purpose, we examined endomyocardial biopsies for the expression of extracellular matrix proteins such as collagens, fibronectin, and an angiogenic growth factor, vascular endothelial growth factor (VEGF), in TF patients with RVH and compared the expression with patients without RVH. Myocardial tissue biopsies were obtained from patients undergoing primary correction (TF-1 group, mean age 0.4 ±0.1 years, n = 8), from those undergoing secondary surgery (TF-2 group, mean age 38.1 ± 3.7 years, n = 6), and from control patients with normal right ventricle (control group, mean age 36.4 ±1.8 years, n = 12). Picro-sirius red staining depicting total collagens and fibronectin staining were semiquantitatively analyzed. Interstitial levels for total collagens were significantly increased in the TF-2 group as compared to the TF-1 group (p < 0.04) and control (p < 0.05) groups. Immunolocalization of fibronectin showed the expression in the interstitium and perivascular areas. Semiquantitative analysis of fibronectin staining revealed that the expression levels were not significandy different in the TF-2 group as compared to the TF-1 and control groups. Angiogenesis, assessed by the increased number of small (p < 0.05) vessels, was observed in both TF groups as compared to the control group. Densitometric analysis of mRNAs encoding VEGF showed significantly enhanced expression in TF-1 (p < 0.02) and TF-2 (p < 0.05) groups as compared to control. Immunoreactive VEGF was localized mainly in the myocytes and smooth muscle cells and not in fibrotic areas in the case of TF groups. Our results show an increased degree of myocardial fibrosis and angiogenesis during RVH in TF patients. This information leaves room for the improvement in contemporary clinical treatment of patients with TF by allowing an assessment of timing for surgery and possibly supports long-term postoperative prognosis.

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Authors and Affiliations

  1. Department of Pharmacology, Erasmus University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands

    Hari S. Sharma & Erik T. H. F. Peters

  2. Department of Thoracic Surgery, Dijkzigt Hospital, Erasmus University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands

    Erik T. H. F. Peters & Ad J. J. C. Bogers

Authors
  1. Hari S. Sharma
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  2. Erik T. H. F. Peters
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  3. Ad J. J. C. Bogers
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Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Aoto Hospital, Jikei University School of Medicine, Tokyo, Japan

    Nobuakira Takeda M.D., Ph.D. (Associate Professor) (Associate Professor)

  2. Jikei University School of Medicine, Tokyo, Japan

    Makoto Nagano M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  3. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla Ph.D., M.D. (Hon.), D.Sc. (Hon) (Distinguished Professor and Director) (Distinguished Professor and Director)

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Sharma, H.S., Peters, E.T.H.F., Bogers, A.J.J.C. (2000). Angiogenesis and Fibrosis During Right Ventricular Hypertrophy in Human Tetralogy of Fallot. In: Takeda, N., Nagano, M., Dhalla, N.S. (eds) The Hypertrophied Heart. Progress in Experimental Cardiology, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4423-4_19

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  • DOI: https://doi.org/10.1007/978-1-4615-4423-4_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6991-2

  • Online ISBN: 978-1-4615-4423-4

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