title: Versican is induced in infiltrating monocytes in myocardial infarction.
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.
authors.affiliation: Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Toeda
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirohata
authors.forename: Omer F
authors.initials: OF
authors.lastname: Hatipoglu
authors.forename: Kadir
authors.initials: K
authors.lastname: Demircan
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ogawa
authors.forename: Shozo
authors.initials: S
authors.lastname: Kusachi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology*; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D015850:Interleukin-6; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C508322:VCAN protein, human; C508324:Vcan protein, rat; D053675:Versicans; D016178:Granulocyte-Macrophage Colony-Stimulating Factor