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Smad Cofactors/Corepressors in the Fibrosed Post-MI Heart: Possible Therapeutic Targets

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Pathophysiology of Cardiovascular Disease

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 10))

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Summary

Several axioms that govern our understanding of the pathogenesis of post-MI congestive heart failure have recently been questioned or revisited in lieu of the relative flood of new data addressing the role of cardiac non-myocytes in this disease state. Among these is the assumption that the cardiac matrix necessarily serves a secondary role to initial progressive dysfunction of cardiac myocytes. It is now well established that remodeling of the cardiac interstitium is a separate and distinct contributor to the progression to heart failure, and that the turnover of extracellular matrix is rapid enough to be relevant to progressive heart disease. As cardiac fibroblasts and myofibroblasts are the main source of matrix and regulate cardiac wound healing, the study of stimulating ligands and their signaling pathways may reveal novel sites for therapeutic intervention. This chapter provides background on the cardiac interstitial components and their turnover as well as providing support for the argument for the need to address post-receptor components of classical TGF-ß signaling in the regulation of cardiac (myo)fibroblast function, with an emphasis on Smad proteins and their cofactors/corepressors.

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Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and the Department of Physiology, University of Manitoba, Winnipeg, Canada

    Julie C. Roth, Baiqiu Wang, Darren H. Freed & Ian M. C. Dixon PhD (Associate Professor of Physiology)

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  1. Julie C. Roth
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  2. Baiqiu Wang
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  3. Darren H. Freed
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  4. Ian M. C. Dixon PhD
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Correspondence to Ian M. C. Dixon PhD .

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Editors and Affiliations

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

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Distinguished Professor and Director)

  2. Philipps University of Marburg, Marburg, Germany

    Heinz Rupp PhD (Professor of Medicine) (Professor of Medicine)

  3. Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Aubie Angel MD (Professor of Internal Medicine) (Professor of Internal Medicine)

  4. Division of Stroke & Vascular Disease St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

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Roth, J.C., Wang, B., Freed, D.H., Dixon, I.M.C. (2004). Smad Cofactors/Corepressors in the Fibrosed Post-MI Heart: Possible Therapeutic Targets. In: Dhalla, N.S., Rupp, H., Angel, A., Pierce, G.N. (eds) Pathophysiology of Cardiovascular Disease. Progress in Experimental Cardiology, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0453-5_34

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