Thrombospondin-1 is induced in rat myocardial infarction and its induction is accelerated by ischemia/reperfusion

Exp Biol Med (Maywood). 2005 Oct;230(9):621-30. doi: 10.1177/153537020523000904.


Thrombospondin-1 (TSP-1) is a multifunctional, rapid-turnover matricellular protein. Recent studies demonstrated that TSP-1 has a role in regulating inflammatory reactions. Myocardial infarction (MI) is associated with an inflammatory response, ultimately leading to healing and scar formation. In particular, an enhanced inflammatory reaction and a massive accumulation of monocytes/macrophages is seen with reperfusion after MI. To examine the role of TSP-1 in MI, we isolated rat TSP-1 complementary DNA (cDNA) and analyzed the level and distribution of the mRNA expression. In infarcted rat hearts, TSP-1 mRNA increased markedly at 6 and 12 hrs after coronary artery ligation (27.97 +/- 3.40-fold and 22.77 +/- 1.83-fold, respectively, compared with sham-operated hearts). Western blot analysis revealed that TSP-1 protein was transiently induced in the infarcted heart. Using in situ hybridization analysis, TSP-1 mRNA signals were observed in the infiltrating cells at the border area of infarction. We then examined the effect of ischemia/reperfusion (I/R) on TSP-1 mRNA induction in the rats with infarcted hearts. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that I/R enhanced the TSP-1 mRNA expression approximately 4-fold, as compared with the level in the permanently ligated heart. Finally, we examined the effect of TSP-1 on proinflammatory cytokine release in mononuclear cells. The releases of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) from human mononuclear cells were enhanced by TSP-1 in a dose-dependent manner. Thus, the immediate and marked increase of TSP-1 expression suggests that TSP-1 has an inflammatory-associated role in MI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Molecular Sequence Data
  • Myocardial Infarction / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thrombospondin 1 / biosynthesis*
  • Thrombospondin 1 / chemistry
  • Thrombospondin 1 / genetics


  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • Thrombospondin 1

Associated data

  • GENBANK/AF309630