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Matrix Metalloproteinases Repress Hypertrophic Growth in Cardiac Myocytes

Gerhild Euler1, Fabian Locquet2, Joanna Kociszewska2

  • 1Institute of Physiology, Justus-Liebig-Universität Giessen, Aulweg 129, 35392, Giessen, Germany. Gerhild.Euler@physiologie.med.uni-giessen.de.

Cardiovascular Drugs and Therapy
|January 5, 2021
PubMed
Abstract

Insights

Inhibition of matrix metalloproteinases (MMPs) promotes cardiac hypertrophy in rat heart cells. MMPs in healthy hearts may normally repress this hypertrophic growth.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs) are known extracellular matrix modulators in heart failure.
  • Emerging evidence suggests intracellular roles and varied effects (pro- and anti-hypertrophic) of MMPs in the heart.
  • Different MMP sources in cardiac tissue may explain these diverse effects.

Purpose of the Study:

  • To investigate the role of matrix metalloproteinases (MMPs) in the hypertrophic growth of isolated rat ventricular cardiac myocytes.
  • To determine if MMPs influence cardiac myocyte size and protein synthesis.

Main Methods:

  • Isolated rat ventricular cardiomyocytes were used for experiments.
  • Gene expression (RT-qPCR), protein levels (western blots), and enzyme activity (zymography) of MMPs were analyzed.
  • Hypertrophic growth was assessed by measuring cardiomyocyte cross-sectional area and protein synthesis rate.

Main Results:

  • MMP-1, MMP-2, MMP-3, MMP-9, and MMP-14 mRNAs were detected in cardiomyocytes; protein expression of MMP-2, MMP-9, and MMP-14 was confirmed.
  • Hypertrophic stimulation led to decreased MMP expression, suggesting MMP downregulation promotes hypertrophy.
  • Inhibition of MMPs (using TAPI-0, TIMP2, or ARP-100) enhanced hypertrophic growth.
  • TAPI-0 treatment activated ERK and Akt signaling pathways and inhibited GSK3β, which were crucial for the observed hypertrophic growth.

Conclusions:

  • Inhibition of matrix metalloproteinases (MMPs) promotes hypertrophic growth in cardiomyocytes in vitro.
  • MMPs in healthy hearts may play a crucial role in preventing cardiac hypertrophy.
Keywords:
CardiomyocytesHypertrophyMatrix metalloproteinaseSignaling kinases

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