Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia

Manoj M Lalu1, Tamás Csont, Richard Schulz

  • 1Department of Pharmacology, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.

Abstract

Insights

Endotoxemia alters matrix metalloproteinase (MMP) activity in the heart and plasma. Increased plasma MMP-9 may contribute to cardiovascular dysfunction during endotoxemia.

Area of Science:

  • Cardiovascular Physiology
  • Biochemistry
  • Animal Models

Background:

  • Endotoxemia is a serious condition characterized by systemic inflammation and cardiovascular dysfunction.
  • Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling and inflammation, but their role in endotoxemia is not fully understood.

Purpose of the Study:

  • To investigate alterations in myocardial and plasma matrix metalloproteinase (MMP) activities during endotoxemia.
  • To explore the relationship between MMP activity changes and cardiovascular dysfunction in endotoxemia.

Main Methods:

  • A prospective randomized animal study was conducted using male Sprague-Dawley rats.
  • Rats were administered bacterial lipopolysaccharide (LPS) or vehicle, with samples collected at various time points post-administration.
  • Heart and plasma samples were analyzed for MMP-2 and MMP-9 activity using gelatin zymography and immunoblotting.

Main Results:

  • LPS administration significantly depressed blood pressure starting at 3 hours, with peak effects at 6-12 hours.
  • Myocardial MMP-2 activity decreased significantly during peak endotoxemia.
  • Plasma MMP-2 activity decreased, while plasma MMP-9 activity rapidly increased and correlated inversely with blood pressure.

Conclusions:

  • Endotoxemia induces rapid changes in both myocardial and plasma MMP activities.
  • Elevated circulating MMP-9 activity is a potential contributor to cardiovascular dysfunction observed in endotoxemia.

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