Key result
Exercise training attenuates heart failure progression by activating cardiomyocyte autophagy via lncRNA NEAT1 downregulation.
Why the study?
The lncRNA NEAT1 is involved in HF progression and is regulated by exercise in muscle tissue, but whether exercise influences HF progression by regulating NEAT1 expression and its underlying molecular mechanisms were unknown.
Does exercise training attenuate heart failure progression by regulating the ILF3/lncRNA NEAT1 axis and cardiomyocyte autophagy in rat models of heart failure?
Does exercise training attenuate heart failure progression by regulating the ILF3/lncRNA NEAT1 axis and cardiomyocyte autophagy in rat models of heart failure?
This preclinical study identifies the ILF3/lncRNA NEAT1/PI3K/AKT/mTOR autophagy axis as a molecular mechanism through which exercise training ameliorates heart failure progression.
Answers are grounded in this paper and cite their sources.
May support exercise-mediated autophagy in preclinical HF; leaves open translation to human therapies or trials.
Heart failure (HF) is a common cardiovascular disease. It has been reported that the lncRNA NEAT1 is involved in the progression of HF and that exercise can regulate the expression of NEAT1 in muscle tissue. This study aimed to investigate whether exercise can influence HF progression by regulating NEAT1 expression and to elucidate its molecular mechanisms. Two independent rat HF models were established separately by intraperitoneal injection of isoproterenol hydrochloride (ISO) or by abdominal aortic constriction (AAC), whereas an in vitro HF model was induced by angiotensin II (Ang-II) in rat H9c2 cardiomyocytes. After 4 weeks of exercise training, serum NT-pro BNP levels were measured in the rats, and cardiac injury was assessed via HE staining and Masson staining. The expression of key genes and proteins was detected using RT‒qPCR, Western blotting, and immunofluorescence, and apoptosis was evaluated via TUNEL staining. RNA immunoprecipitation experiments were performed to validate the interaction between NEAT1 and ILF3. NEAT1 expression is upregulated in HF, and its knockdown can inhibit cellular damage in in vitro and in vivo HF models and improve cardiac function in rats. Additionally, exercise training reduces the expression of NEAT1 in the cardiac tissues of HF rats, and overexpression of NEAT1 weakens the inhibitory effect of exercise training on the progression of HF in rats, indicating that exercise training improves HF progression by suppressing NEAT1 expression. Mechanistic studies revealed that upregulated ILF3 in HF binds to NEAT1 to stabilize its expression, thereby activating the PI3K/AKT/mTOR signaling pathway, which subsequently inhibits autophagy, ultimately leading to HF. Exercise training can downregulate NEAT1 expression, thereby suppressing abnormal activation of the PI3K/AKT/mTOR signaling pathway and further relieving HF progression through the activation of autophagy. Additionally, NEAT1 expression is regulated by ILF3.
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Zhang et al. (2026) studied Heart failure (in vivo rat models induced by isoproterenol hydrochloride or abdominal aortic constriction; in vitro rat H9c2 cardiomyocyte model induced by angiotensin II). Exercise training and lncRNA NEAT1 knockdown/overexpression vs. Untreated heart failure control models and NEAT1 overexpression was evaluated on Heart failure progression, cardiac injury, serum NT-proBNP levels, apoptosis, and PI3K/AKT/mTOR signaling-mediated cardiomyocyte autophagy. Four weeks of exercise training improved heart failure progression in rats by downregulating lncRNA NEAT1, inhibiting PI3K/AKT/mTOR signaling, and activating cardiomyocyte autophagy.
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