Tamoxifen treatment of myocardial infarcted female rats exacerbates scar formation

  • Pedro Geraldes
  • Hugues Gosselin
  • Jean-François Tanguay
  • Robert Clément
  • Angelino Calderone
Cardiovascular System

Abstract

Hormonal replacement therapy in postmenopausal women was associated with an increased incidence of nonfatal myocardial infarction. Selective estrogen receptor modulators were considered an alternative pharmacological approach. However, selective estrogen receptor modulators acting via estrogen receptor-dependent and receptor-independent mechanisms may negatively influence cardiac remodeling. The present study tested the hypothesis that tamoxifen (TAM) treatment after coronary artery ligation compromised scar formation. TAM administration (10 mg kg−1 day−1 for 3 weeks) to postmyocardial infarcted (MI) female adult rats significantly increased scar surface area (TAM+MI = 0.67 ± 0.08 vs MI = 0.45 ± 0.06 cm2) and weight (TAM+MI = 0.071 ± 0.007 vs MI = 0.050 ± 0.006 grams). In the infarct region, a significant decrease (p < 0.05) of small calibre vessels (lumen diameter <50 μm) was observed in TAM treated post-MI rats (4.5 ± 0.8 vessels/mm2), as compared to untreated MI rats (7 ± 0.7 vessels/mm2). Consistent with the latter finding, 4-OH TAM caused a dose-dependent suppression of vascular endothelial growth factor (VEGF)-stimulated (10−9 mol/l) capillarity-like tubule formation by rat aortic endothelial cells in vitro via an estrogen receptor-independent mechanism. These data have demonstrated that TAM treatment of post-MI female rats exacerbated scar formation and may have occurred at least in part via the attenuation of new vessel formation in the infarct region.

Keywords

Heart Ischemia Vessels Reparative fibrosis 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Pedro Geraldes
    • 1
    • 2
  • Hugues Gosselin
    • 1
  • Jean-François Tanguay
    • 1
    • 2
  • Robert Clément
    • 1
  • Angelino Calderone
    • 1
    • 3
  1. 1.Research CentreMontreal Heart InstituteMontrealCanada
  2. 2.Department of MedicineUniversité de MontréalMontrealCanada
  3. 3.Departement de PhysiologieUniversité de MontréalMontrealCanada

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