Cardiac-specific Trim44 knockout in rat attenuates isoproterenol- induced cardiac remodeling via inhibition of AKT/mTOR pathway

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and knockout rats were generated using CRISPR-Cas9 technology. affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3 & beta;/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.

Automated summary

When pathological hypertrophy progresses to heart failure, the prognosis is often very poor. A study using Trim44 knockout rats generated through CRISPR-Cas9 technology found that Trim44 deficiency protected against cardiac pathological changes and reduced myocardial fibrosis in response to isoproterenol treatment. The study also demonstrated that Trim44 deficiency inhibited signaling pathways involved in myocardial hypertrophy, suggesting it as a potential therapeutic target for preventing cardiac hypertrophy and heart failure.