Ciliary neurotrophic factor attenuates myocardial infarction-induced oxidative stress and ferroptosis via PI3K/Akt signaling.

backgroundAs a member of the interleukin-6 family, ciliary neurotrophic factor (CNTF) regulates inflammation, oxidative stress, and other processes to exhibit neurotrophic and differentiating effects over cells in the central nervous system. It has not yet been documented, therefore, if CNTF influences the cardiac remodeling brought on by myocardial infarction (MI). The purpose of the current investigation was to identify the function and underlying mechanisms of CNTF in cardiac remodeling brought on by MI.

methodsUsing an adeno-associated virus 9 (AAV9) system and tail vein injection, we overexpressed CNTF in the hearts. To create a model of MI, C57BL/6 mice underwent left anterior descending (LAD) ligation. The following techniques were employed to assess the impact of CNTF overexpression and the underlying mechanisms: quantitative real-time PCR, western blotting, histological analysis, immunofluorescence and immunohistochemistry analysis, and echocardiography. We used H9c2 cells to confirm CNTF's in vitro effects.

resultsIn MI mice, overexpression of CNTF prevents cardiac hypertrophy and cardiac fibrosis. Furthermore, oxidative stress and ferroptosis in response to MI damage were markedly reduced by CNTF overexpression. Mechanistically, overexpression of CNTF in both in vivo and in vitro markedly enhanced PI3K/Akt signaling. However, blocking this pathway effectively negated the beneficial impact of CNTF overexpression.

conclusionsOur research indicates that via initiating the PI3K/Akt signaling pathway, CNTF controls myocardial dysfunction, oxidative stress, and ferroptosis in MI-induced cardiac remodeling. CNTF may have therapeutic potential in treating MI-induced cardiac remodeling.