Recurrent Myocardial Injury Leads to Disease Tolerance in a Murine Model of Stress-Induced Cardiomyopathy

Sajal K. Tiwary, Tomohiro Hayashi, Attila Kovacs, Douglas L. Mann

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Whereas the innate immune response to an initial episode of cardiac injury has been studied extensively, the response of the immune system to recurrent cardiac tissue injury is not well understood. Specifically, it is not known whether the immune system adapts to the initial episode of cardiac injury and whether any adaptations that occur lead to immune cell hypo-responsiveness or, alternatively, immune cell hyper-responsiveness. Here, we studied the role of adrenergic-mediated stress using a simple model of reversible stress-induced cardiomyopathy, and show that isoproterenol-induced tissue injury and inflammation are sufficient to protect the heart from the myopathic effects of a subsequent exposure to isoproterenol. Remarkably, pharmacological depletion of macrophages partially attenuated the isoproterenol-induced cytoprotective response, suggesting that immune-mediated tissue repair mechanisms confer tolerance to subsequent tissue damage.

Original languageEnglish
Pages (from-to)783-797
Number of pages15
JournalJACC: Basic to Translational Science
Issue number7
StatePublished - Jul 2023


  • inflammation
  • preconditioning
  • tissue injury


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