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Cardiac Fibrosis During the Development of Heart Failure: New Insights into Smad Involvement

  • Chapter
Book cover Cardiac Development

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 4))

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Summary

Angiotensin II (angiotensin) and transforming growth factor-β1 (TGF-β1) play an important role in cardiac fibrosis and infarct scar remodeling after myocardial infarction (MI). We characterized 8 week post-MI rat hearts for altered expression of Smad proteins with and without losartan treatment. AT1 blockade was associated with attenuated activation of the latent form of TGF-β1 in remnant (viable) myocardium and infarct scar. Immunofluorescence (IF) studies revealed Smad 2 localization to myofibroblasts in target tissues with less intense staining in cardiac myocytes. Losartan administration (15mg/kg/day) for 8 weeks was associated with normalization of total cellular Smad 2 and Smad 4 overexpression in the infarct scar as well as Smad 2 overexpression in remnant heart tissue. On the other hand, phosphorylated Smad 2 (P-Smad 2) staining was reduced in cytosolic fractions from failing experimental heart tissues vs controls and these trends were normalized in the presence of losartan, suggesting augmented P-Smad 2 movement into nuclei in untreated hearts. Using cultured adult primary rat fibroblasts treated with 10-6M angiotensin, we noted rapid translocation (15 min) of P-Smad 2 into the cellular nuclei from the cytosol. Nuclear P-Smad 2 protein levels were increased in cultured fibroblasts following 15 min angiotensin treatment, and this response was blocked by losartan treatment. We conclude that angiotensin may influence total Smad 2 and 4 expression in post-MI heart failure, and that angiotensin treatment is associated with rapid P-Smad 2 nuclear translocation in isolated fibroblasts. This study suggests that crosstalk between angiotensin and Smad signaling are associated with fibrotic events in post-MI hearts.

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Authors and Affiliations

  1. Laboratory of Molecular Cardiology, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, 351 Tache Avenue, Winnipeg, R2H 2A6, Manitoba, Canada

    Hao Jianming, Wang Baiqiu, Stephen C. Jones & Ian M. C. Dixon Ph.D.

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  1. Hao Jianming
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  2. Wang Baiqiu
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  3. Stephen C. Jones
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  4. Ian M. C. Dixon Ph.D.
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Correspondence to Ian M. C. Dixon Ph.D. .

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Editors and Affiliations

  1. Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Bohuslav Ostadal M.D., D.Sc. (Professor) (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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Jianming, H., Baiqiu, W., Jones, S.C., Dixon, I.M.C. (2002). Cardiac Fibrosis During the Development of Heart Failure: New Insights into Smad Involvement. In: Ostadal, B., Nagano, M., Dhalla, N.S. (eds) Cardiac Development. Progress in Experimental Cardiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0967-7_7

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  • DOI: https://doi.org/10.1007/978-1-4615-0967-7_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5328-7

  • Online ISBN: 978-1-4615-0967-7

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