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Role of Chymase in Matrix and Myocardial Remodeling Due to Mitral Regurgitation: Implications for Therapy

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Cardiac Remodeling

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 5))

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Abstract

The pure volume overload of mitral regurgitation (MR) has many unique features including matrix metalloproteinase (MMP) activation, increased bradykinin, extracellular matrix loss, disruption of the focal adhesion complex, and cardiomyocyte myofibrillar loss—all of which either directly or indirectly are beneficially affected by inhibition of chymase. Cardiomyocyte myofibrillar loss and cytoskeletal disruption may be related to intracellular oxidative stress and/or increased chymase production within the cardiomyocyte. Increased adrenergic drive is also an important underlying pathophysiologic feature, which, like chymase activation, is present both early and late in course of MR. There is now both dog and human data ­demonstrating the benefit of β1-receptor blockade in isolated MR. However, neither ­chymase inhibition nor β1-receptor blockade alone attenuates left ventricular (LV) dilatation. These data raise the intriguing question whether the combination of a chymase inhibitor and β1-receptor blocker would have a synergistic effect in preventing LV remodeling, especially if started early in the course of isolated MR.

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Acknowledgments

This study is supported by the Office of Research and Development, Medical Service, Department of Veteran Affairs (LJD), and Specialized Centers of Clinically Orientated Research grant in Cardiac Dysfunction P50HL077100 and in part by Teijin Pharmaceuticals Ltd, Tokyo, Japan (LJD).

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Authors and Affiliations

  1. Birmingham Veteran Affairs Medical Center, University of Alabama at Birmingham, 434 BMRII, 901 19th Street South, Birmingham, AL, 35294-2180, USA

    Spencer J. Melby

  2. Department of Cardiovascular Surgery, University of Alabama Medical Center, Alabama, AL, 35294, USA

    Spencer J. Melby

  3. UAB Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Spencer J. Melby & Chih-Cheng Wei

  4. Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Carlos M. Ferrario

  5. Division of Cardiovascular Disease, Department of Medicine, Birmingham Veteran Affairs Medical Center, University of Alabama at Birmingham, 434 BMRII, 901 19th Street South, Birmingham, AL, 35294-2180, USA

    Chih-Cheng Wei & Louis J. Dell’Italia M.D.

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  1. Spencer J. Melby
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  2. Carlos M. Ferrario
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  3. Chih-Cheng Wei
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  4. Louis J. Dell’Italia M.D.
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Corresponding author

Correspondence to Louis J. Dell’Italia M.D. .

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Editors and Affiliations

  1. Walter MacKenzie Health Sciences Centre, Division of Cardiology, University of Alberta, 8440-112 Street, Edmonton, T6G 2B7, Alberta, Canada

    Bodh I. Jugdutt

  2. St. Boniface General Hospital Research C, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Melby, S.J., Ferrario, C.M., Wei, CC., Dell’Italia, L.J. (2013). Role of Chymase in Matrix and Myocardial Remodeling Due to Mitral Regurgitation: Implications for Therapy. In: Jugdutt, B., Dhalla, N. (eds) Cardiac Remodeling. Advances in Biochemistry in Health and Disease, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5930-9_12

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