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

  • Spencer J. Melby
  • Carlos M. Ferrario
  • Chih-Cheng Wei
  • Louis J. Dell’Italia
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 5)


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.


Mitral regurgitation Volume overload Chymase Matrix metalloproteinase Focal adhesion kinase 



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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Spencer J. Melby
    • 1
    • 2
    • 3
  • Carlos M. Ferrario
    • 4
  • Chih-Cheng Wei
    • 5
    • 3
  • Louis J. Dell’Italia
    • 5
  1. 1.Birmingham Veteran Affairs Medical Center, University of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Cardiovascular SurgeryUniversity of Alabama Medical CenterAlabamaUSA
  3. 3.UAB Comprehensive Cardiovascular CenterUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Wake Forest University School of MedicineWinston-SalemUSA
  5. 5.Division of Cardiovascular Disease, Department of MedicineBirmingham Veteran Affairs Medical Center, University of Alabama at BirminghamBirminghamUSA

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