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WenLi Yuan
SourceMedical Cube Pro
Medicine Cube ProOn a global scale, heart failure is the main cause of death, and the number of deaths caused by heart failure even exceeds the total number of deaths caused by all cancers
Previous studies have shown that the activity of the Hippo signaling pathway in patients with heart failure will increase.
On June 30, researchers from Baylor College of Medicine and Texas Heart Research Institute published their latest research in the field of heart failure gene therapy in Science Translational Medicine
Source: Science Translational Medicine
The research team turned off the Hippo signaling pathway in a mouse model that mimics human heart failure in the early days, and found that the mouse heart restored its pumping function, so the researchers wanted to explore whether turning off the Hippo signaling pathway has the same effect in the pig heart
In this study, they used AAV9 gene therapy to locally knock down the Hippo pathway gene Salvador (Sav) in the cardiomyocytes of the border zone in a pig model of myocardial infarction.
Two weeks after myocardial infarction, when pigs developed left ventricular systolic dysfunction, the researchers injected AAV9-Sav-short hairpin RNA (shRNA) or a control AAV9 vector carrying green fluorescent protein (GFP) directly into cardiomyocytes in the border zone
AAV9-Sav-shRNA gene therapy improves heart function in pigs with myocardial infarction (Source: Science Translational Medicine)
Three months after injection, the ejection fraction (a measure of left ventricular systolic function) of the pig heart treated with high-dose AAV9-Sav-shRNA increased by 14.
Proliferation of porcine cardiomyocytes injected with AAV9-Sav shRNA increases after myocardial infarction (Source: Science Translational Medicine)
In addition, AAV9-Sav-shRNA gene therapy is well tolerated and does not cause death.
The corresponding author of the paper, Dr.
Reference materials:
[1] Shi JL et al.
[2] Novel gene therapy for heart failure closer to the clinic (Source: Baylor College of Medicine)