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Increased expression and activity of matrix metalloproteinases characterize embolic cardiac myxomas

Augusto Orlandi1, Alessandro Ciucci, Amedeo Ferlosio

  • 1Department of Anatomic Pathology, Tor Vergata University of Rome Via Montpellier 1, Rome, Italy. orlandi@uniroma2.it

The American Journal of Pathology
|May 28, 2005
PubMed

Insights

Matrix metalloproteinases (MMPs) contribute to cardiac myxoma tumor embolism by degrading extracellular matrix. Overexpression of specific MMPs in embolic myxomas suggests a key role in this process.

Area of Science:

  • Cardiovascular Pathology
  • Molecular Biology
  • Oncology

Background:

  • Tumor embolism is a frequent complication of cardiac myxoma, yet its underlying mechanisms remain unclear.
  • Matrix metalloproteinases (MMPs) are implicated in matrix degradation and tissue remodeling, relevant to various pathologies including cancer and cardiovascular diseases.

Purpose of the Study:

  • To investigate the role of MMPs in tumor embolism associated with cardiac myxomas.
  • To determine if MMP expression and activity are elevated in myxomas prone to embolism.

Main Methods:

  • Analysis of 27 left atrium-sided myxomas (10 embolic, 17 non-embolic) using immunohistochemistry, Western blotting, and zymography.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) to assess MMP and TIMP gene expression.
  • In vitro studies on embolic tumor cells stimulated with cytokines.

Main Results:

  • Embolic myxomas exhibited higher expression and activity of MT1-MMP, pro-MMP-2, and pro-MMP-9 compared to non-embolic tumors.
  • Increased MMP activity was linked to enhanced gene transcription and elevated TIMP-2 transcripts in embolic myxomas.
  • Embolic tumor cells showed higher basal and cytokine-stimulated MT1-MMP and pro-MMP-2 levels, correlating with increased extracellular matrix degradation.

Conclusions:

  • Matrix metalloproteinase (MMP) overexpression is strongly associated with increased extracellular matrix degradation in cardiac myxomas.
  • Elevated MMP activity likely contributes to an increased risk of tumor embolism in cardiac myxoma patients.

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