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

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The pure volume overload of mitral régurgitation (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 ß1-receptor blockade in isolated MR. However, neither chymase inhibition nor ß1-receptor blockade alone attenuates left ventricular (LV) dilatation. These data raise the intriguing question whether the combination of a chymase inhibitor and ß1-receptor blocker would have a synergistic effect in preventing LV remodeling, especially if started early in the course of isolated MR.

Original languageEnglish
Title of host publicationCardiac Remodeling
Subtitle of host publicationMolecular Mechanisms
PublisherSpringer New York
Pages201-214
Number of pages14
ISBN (Electronic)9781461459309
ISBN (Print)9781461459293
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Chymase
  • Focal adhesion kinase
  • Matrix metalloproteinase
  • Mitral regurgitation
  • Volume overload

Fingerprint Dive into the research topics of 'Role of chymase in matrix and myocardial remodeling due to mitral regurgitation: Implications for therapy'. Together they form a unique fingerprint.

  • Cite this

    Melby, S. J., Ferrario, C. M., Wei, C. C., & Dell'Italia, L. J. (2013). Role of chymase in matrix and myocardial remodeling due to mitral regurgitation: Implications for therapy. In Cardiac Remodeling: Molecular Mechanisms (pp. 201-214). Springer New York. https://doi.org/10.1007/978-1-4614-5930-9_12