Change in the cells that express connective tissue growth factor in acute Coxsackievirus-induced myocardial fibrosis in mouse

Virus Res. 2007 Jun;126(1-2):62-8. doi: 10.1016/j.virusres.2007.01.016. Epub 2007 Mar 12.

Abstract

Cardiac fibrosis and inflammation are major pathologic conditions that result from viral myocarditis. Connective tissue growth factor (CTGF) stimulates fibroblast proliferation and induces production of extracellular matrix molecules. We studied the correlation between CTGF and cardiac fibrosis in an acute Coxsackievirus B3 (CVB3) myocarditis animal model. Eight-week-old BALB/c mice were infected intraperitoneally with 10(4) plaque forming units (PFU) of CVB3. Myocardial inflammation peaked on day 7 and decreased markedly by day 14 post-infection (pi); cardiac fibrosis was noted from day 7 and peaked on day 14. By contrast, CTGF was weakly expressed by the interstitial cells in uninfected control hearts and also in the hearts of day 3 pi. CTGF expression measured by real-time PCR was elevated on day 3 and peaked on day 7 pi. TGF-beta expression peaked at day 7 pi. The cell type of CTGF expression changed from interstitial cells to myocytes after virus infection. On day 7, CTGF was strongly expressed by myocytes and inflammatory cells surrounding calcified necrotic areas. In addition, cardiac myocytes expressed CTGF on day 14. Our results, based on an acute CVB3 model of myocarditis, provide evidence that CTGF may mediate the development of fibrosis after viral myocarditis, and that the cells expressed CTGF changes during the course of viral myocarditis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Base Sequence
  • Collagen Type I / genetics
  • Connective Tissue Growth Factor
  • Coxsackievirus Infections / genetics*
  • Coxsackievirus Infections / metabolism
  • Coxsackievirus Infections / pathology
  • DNA Primers / genetics
  • Enterovirus B, Human / pathogenicity*
  • Female
  • Fibrosis
  • Gene Expression
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / genetics*
  • Myocarditis / metabolism
  • Myocarditis / pathology
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tissue Distribution
  • Transforming Growth Factor beta / genetics

Substances

  • CCN2 protein, mouse
  • Collagen Type I
  • DNA Primers
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor