VSNL1 attenuates hypoxia‑induced myocardial apoptosis by regulating the CNP/NPRB pathway

Myocardial apoptosis is a key contributor to the pathogenesis of cardiovascular diseases, driving cardiac dysfunction and disease progression. Visinin‑like protein 1 (VSNL1), a protein involved in cardiac pacing and tumor cell apoptosis, may serve a role in myocardial apoptosis. However, its specific function and underlying mechanisms remain unclear. The present study aimed to elucidate the role and molecular pathways of VSNL1 in myocardial apoptosis. Using a hypoxia‑induced AC16 cardiomyocyte model, combined with cell transfection, western blotting and biochemical kit detection, a time‑dependent decrease in VSNL1 expression was observed under hypoxic conditions. Overexpression of VSNL1 markedly attenuated hypoxia‑induced apoptosis, accompanied by a reduction in myocardial injury markers such as malonaldehyde, creatine kinase‑MB and lactate dehydrogenase. Furthermore, VSNL1 inhibited excessive reactive oxygen species production and preserved the mitochondrial membrane potential during the early phase of myocardial apoptosis. Conversely, knockdown of VSNL1 exacerbated hypoxia‑induced apoptosis, elevated oxidative stress and aggravated mitochondrial dysfunction in cardiomyocytes. Mechanically, VSNL1 was demonstrated to alleviate myocardial apoptosis by upregulating the 2',3'‑cyclic nucleotide 3' phosphodiesterase (CNP)/natriuretic peptide receptor B (NPRB) signaling pathway. Notably, the anti‑apoptosis effects of VSNL1 were partially reversed by silencing of NPRB, underscoring the critical role of this pathway. Co‑immunoprecipitation analysis revealed no direct protein interaction between VSNL1 and CNP, suggesting that VSNL1 regulates the CNP/NPRB pathway through indirect signal transduction rather than physical binding. Furthermore, CNP and NPRB were significantly downregulated at 24 h after permanent ligation of the proximal left anterior descending coronary artery in male C57BL/6 mice and immediately after 24 h of 1% O2 hypoxia in AC16 cardiomyocytes, indicating early suppression of this protective signaling pathway. Collectively, the findings of the present study suggested that VSNL1 could serve as a potential therapeutic target for hypoxia‑induced myocardial apoptosis, providing novel insights into clinical interventions for cardiovascular diseases, particularly in preventing ischemia‑related myocardial injury.