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Tamoxifen treatment of myocardial infarcted female rats exacerbates scar formation

  • Cardiovascular System
  • Published:
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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.

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Acknowledgement

This work was supported by the Heart and Stroke Foundation of Canada and Quebec, Canadian Institutes of Health Research, and “La Fondation de l’Institut de Cardiologie de Montréal.” Dr. Calderone is a “Chercheur-Boursier Senior du Fonds de la recherche en santé du Québec.” Dr. Tanguay and Mr. Geraldes are scholars for the “Fonds de la recherche en santé du Québec.”

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Authors and Affiliations

  1. Research Centre, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec, H1T 1C8, Canada

    Pedro Geraldes, Hugues Gosselin, Jean-François Tanguay, Robert Clément & Angelino Calderone

  2. Department of Medicine, Université de Montréal, Montreal, Quebec, Canada

    Pedro Geraldes & Jean-François Tanguay

  3. Departement de Physiologie, Université de Montréal, Montreal, Quebec, Canada

    Angelino Calderone

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  1. Pedro Geraldes
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  2. Hugues Gosselin
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Correspondence to Angelino Calderone.

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Geraldes, P., Gosselin, H., Tanguay, JF. et al. Tamoxifen treatment of myocardial infarcted female rats exacerbates scar formation. Pflugers Arch - Eur J Physiol 454, 385–393 (2007). https://doi.org/10.1007/s00424-007-0215-5

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  • DOI: https://doi.org/10.1007/s00424-007-0215-5

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