Versican is induced in infiltrating monocytes in myocardial infarction

Mol Cell Biochem. 2005 Dec;280(1-2):47-56. doi: 10.1007/s11010-005-8051-4.

Abstract

Versican, a large chondroitin sulfate proteoglycan, plays a role in conditions such as wound healing and tissue remodelling. To test the hypothesis that versican expression is transiently upregulated and plays a role in the infarcted heart, we examined its expression in a rat model of myocardial infarction. Northern blot analysis demonstrated increased expression of versican mRNA. Quantitative real-time RT-PCR analysis revealed that versican mRNA began to increase as early as 6 h and reached its maximal level 2 days after coronary artery ligation. Versican mRNA then gradually decreased, while the mRNA of decorin, another small proteoglycan, increased thereafter. Versican mRNA was localized in monocytes, as indicated by CD68-positive staining, around the infarct tissue. The induction of versican mRNA was accelerated by ischemia/reperfusion (I/R), which was characterized by massive cell infiltration and enhanced inflammatory response. To examine the alteration of versican expression in monocytes/macrophages, we isolated human peripheral blood mononuclear cells and stimulated them with granulocyte/macrophage colony-stimulating factor (GM-CSF). Stimulation of mononuclear cells with GM-CSF increased the expression of versican mRNA as well as cytokine induction. The production of versican by monocytes in the infarct area represents a novel finding of the expression of an extracellular matrix gene by monocytes in the infarcted heart. We suggest that upregulation of versican in the infarcted myocardium may have a role in the inflammatory reaction, which mediates subsequent chemotaxis in the infarcted heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Chondroitin Sulfate Proteoglycans / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • In Situ Hybridization
  • Interleukin-6 / biosynthesis
  • Lectins, C-Type / genetics*
  • Male
  • Monocytes / metabolism*
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / immunology*
  • Myocardial Ischemia
  • Myocardial Reperfusion
  • Myocardium / pathology
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation*
  • Versicans

Substances

  • Chondroitin Sulfate Proteoglycans
  • Interleukin-6
  • Lectins, C-Type
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • VCAN protein, human
  • Vcan protein, rat
  • Versicans
  • Granulocyte-Macrophage Colony-Stimulating Factor