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Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse
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AAV9-mediated functional screening for cardioprotective cytokines in Coxsackievirus-B3-induced myocarditis

Paolo Carai1,2, Giulia Ruozi3, Alexandra Paye2

  • 1Department of Cardiovascular Sciences, Center for Vascular and Molecular Biology, KU Leuven, Leuven, Belgium.

Scientific Reports
|May 4, 2022
PubMed

Insights

Researchers identified five cardioprotective cytokines, including IL9, to combat viral myocarditis (VM). These factors reduced heart inflammation and damage in a mouse model, offering potential new treatments for heart failure caused by VM.

Area of Science:

  • Immunology
  • Cardiology
  • Molecular Biology

Background:

  • Viral myocarditis (VM) is a significant cause of heart failure (HF).
  • The molecular mechanisms driving cardiac inflammation and cardiomyocyte necrosis in VM are not fully understood.
  • Effective cardioprotective agents for VM are currently lacking.

Purpose of the Study:

  • To unbiasedly identify novel immunomodulatory molecules with cardioprotective potential in VM.
  • To investigate the efficacy of identified factors in a Coxsackievirus B3 (CVB3)-induced myocarditis mouse model.

Main Methods:

  • Application of an in vivo functional selection (FunSel) method using adeno-associated virus (AAV) vectors.
  • Screening of an expression library containing 60 cytokines through two rounds of in vivo FunSel.
  • Utilizing a CVB3-induced mouse model of viral myocarditis.

Main Results:

  • Five cardioprotective cytokines (IL9, IL3, IL4, IL13, IL15) were identified.
  • Three detrimental cytokines (IL18, IL17b, CCL11) were counter-selected.
  • Pooled overexpression of the five protective cytokines reduced inflammation and cardiac dilatation for at least one month.
  • Individual overexpression of IL9 significantly reduced cardiac inflammation and injury, shifting immune cell balance towards anti-inflammatory phenotypes.

Conclusions:

  • AAV9-mediated functional selection is an effective strategy for identifying cardioprotective factors in VM.
  • IL9, IL3, IL4, IL13, and IL15 demonstrate significant cardioprotective effects in a mouse model of CVB3-induced VM.
  • These identified cytokines represent promising therapeutic targets for managing viral myocarditis and preventing heart failure.

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