Tyrphostin AG-556 reduces myocardial infarct size and improves cardiac performance in the rat

Jacob George, Simon Biner, Pnina Keren, Iris Barshack, Iris Goldberg, Jack Sherez, Alexander Levitzki, Gad Keren, Arie Roth

Research output: Contribution to journalArticlepeer-review


TNF-α is a proinflammatory cytokine, abundantly expressed after myocardial infarction. It has been suggested that it exhibits myocardial suppressive and cytotoxic effects. AG-556 is a tyrosine kinase inhibitor synthesized based on its ability to reduce TNF-α production and cell toxicity, and to improve experimental models mediated by TNF-α (i.e., peritontitis and experimental autoimmune encephalomyelitis). Daily, for 7 days, rats were injected ip with either AG-556 dissolved in DMSO or with the control vehicle. Infarct size was determined in the hearts as well as in fibrous scar formation. Cardiac TNF-α expression was evaluated by ELISA and immunohistochemistry. Functional hemodynamic parameters were evaluated employing echocardiography prior to sacrifice. AG-556 treatment reduced MI size at 7 days with a parallel effect on fibrous tissue formation. TNF-α production by splenocytes was reduced upon AG-556 treatment, whereas no differences were evident between the groups with regard to myocardial cytokine expression. AG-556 attenuated the decrease in fractional shortening at the expense of preserving end systolic diameter. AG-556 has proven beneficial in reducing myocardial infarct size and attenuated consequent hemodynamic deterioration in the rat model. If reconfirmed, AG-556 may be of potential clinical use in post-MI patients.

Original languageEnglish
Pages (from-to)314-318
Number of pages5
JournalExperimental and Molecular Pathology
Issue number3
StatePublished - Jun 2003
Externally publishedYes


  • Inflammation
  • Myocardial infarct
  • Rat
  • Remodeling
  • TNF-α


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