paper

• Rat model of chronic IHF

  1. 2-h coronary occlusion followed by reperfusion

  2. 4 weeks later, rats injected intramyocardially with TNNT2-4Fpolycistronic-NIL or LacZ-NIL

  3. 4 months post-viral injection, outcomes assessed
• TNNT2-4Fpolycistronic-NIL gene therapy


  • Induces CM cell cycle re-entry
  • Improves LV function
  • Effects sustained for at least 4 months
• TNNT2-4Fpolycistronic-NIL gene therapy induces CM cell cycle re-entry in chronic IHF and improves LV function
• No reversal of dilatation or adverse remodeling observed
• Transient gene expression targeted to CMs

  Crucial for therapeutic benefits in chronic heart failure
• Improved LV function post-treatment with TNNT2-4Fpolycistronic-NIL
• Scar size and healthy area measured using Masson's trichrome staining
• Immunohistochemistry used to assess heart tissue post-treatment
• Heart failure (HF) is a prevalent syndrome with high morbidity and mortality rates affecting millions worldwide
• Ischaemic heart failure (IHF) is the most common form, resulting from myocardial ischaemia and CM death, leading to adverse structural changes and functional decline
• Chronic IHF remains challenging due to limited CM regeneration capacity, often leading to fibrous tissue replacement and progressive dilatation
• Further research is needed to elucidate the mechanisms and optimize gene therapy strategies for long-term management of heart failure