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Modified hTERT treatment ameliorates pressure overload-induced heart failure - PubMed

2 days ago
  • #Heart Failure
  • #Gene Therapy
  • #Telomerase
  • Heart failure (HF) is an incurable disorder linked to shortened telomeres and cardiomyocyte dysfunction.
  • A modified human telomerase (hTERT) gene therapy (AAV9-modhTERTY707F, D868A) was developed to target HF.
  • The therapy reversed cardiac function decline and prevented fibrosis in mouse models of HF.
  • At the cellular level, modhTERT improved contractile function and calcium handling in cardiomyocytes.
  • modhTERT blocked telomeric DNA damage response (DDR) and reduced p53 phosphorylation.
  • The therapy reduced chronic inflammation and reactive oxygen species (ROS) levels.
  • modhTERT restored mitochondrial structure, increased mtDNA copy number, and boosted ATP production.
  • The study suggests telomere re-protection as a potential gene therapy for HF.
  • Funding was provided by the National Natural Science Foundation of China and other sources.