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

Satoshi Sezaki, Satoshi Hirohata, Akihiro Iwabu, Keigo Nakamura, Kenichi Toeda, Toru Miyoshi, Hitoshi Yamawaki, Kadir Demircan, Shozo Kusachi, Yasushi Shiratori, Yoshifumi Ninomiya

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Abstract

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.

Original languageEnglish
Pages (from-to)621-630
Number of pages10
JournalExperimental Biology and Medicine
Volume230
Issue number9
DOIs
Publication statusPublished - Oct 2005

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Keywords

  • Cytokine
  • Extracellular matrix
  • Gene expression
  • Inflammation
  • Ischemia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sezaki, S., Hirohata, S., Iwabu, A., Nakamura, K., Toeda, K., Miyoshi, T., Yamawaki, H., Demircan, K., Kusachi, S., Shiratori, Y., & Ninomiya, Y. (2005). Thrombospondin-1 is induced in rat myocardial infarction and its induction is accelerated by ischemia/reperfusion. Experimental Biology and Medicine, 230(9), 621-630. https://doi.org/10.1177/153537020523000904