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Selective matrix metalloproteinase inhibition with developing heart failure: effects on left ventricular function and

Mary K King1, Mytsi L Coker, Aaron Goldberg

  • 1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.

Circulation Research
|February 8, 2003
PubMed

Insights

Selective matrix metalloproteinase inhibition (MMPi) improved cardiac function in a heart failure model. This approach, sparing MMP-1, offers a promising therapeutic strategy for congestive heart failure patients.

Area of Science:

  • Cardiovascular Research
  • Biochemistry
  • Pharmacology

Background:

  • Matrix metalloproteinases (MMPs) are implicated in left ventricular (LV) remodeling.
  • Broad-spectrum MMP inhibition, especially of MMP-1, may lack clinical applicability.

Purpose of the Study:

  • To investigate the effects of selective MMP inhibition (sparing MMP-1) in a preclinical model of developing congestive heart failure.

Main Methods:

  • Pigs underwent rapid pacing for 3 weeks to induce heart failure.
  • One group received selective MMP inhibition (PGE7113313) alongside rapid pacing.
  • Control group received no intervention.

Main Results:

  • Selective MMP inhibition reduced elevated LV peak wall stress and improved preload recruitable stroke work compared to rapid pacing alone.
  • Plasma norepinephrine levels were reduced by selective MMPi.
  • Myocyte cross-sectional area increased, while fibrillar collagen volume fraction remained unchanged.

Conclusions:

  • Targeting a selective group of myocardial MMPs represents a rational therapeutic strategy for congestive heart failure.
  • Selective MMP inhibition demonstrates potential benefits in mitigating adverse cardiac remodeling.

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