ABCC9 knockdown attenuates isoproterenol‑induced myocardial hypertrophy by inhibiting the PI3K/AKT signaling pathway.

Myocardial hypertrophy (MH) represents an early pathological manifestation that progresses to severe cardiovascular disease (CVD), and its reversal is important for preventing and treating heart failure. Dysregulated expression of ATP‑binding cassette subfamily C member 9 (ABCC9) has been associated with complex CVD pathogenesis, although its precise mechanistic role remains ambiguous. The present study was designed to investigate the protective effects of ABCC9 knockdown against isoproterenol (ISO)‑induced MH and elucidate its underlying molecular mechanisms. AC16 cardiomyocytes were treated with ISO to establish an MH model, in which ABCC9 protein expression was significantly elevated. Fluorescence staining of cardiomyocyte surface area and quantification of MH‑related biomarkers, including atrial natriuretic peptide, brain natriuretic peptide and β‑myosin heavy chain, demonstrated that ABCC9 knockdown effectively attenuated MH and improved cardiac function. Furthermore, western blot analysis and flow cytometry revealed that ABCC9 knockdown not only decreased cardiomyocyte apoptosis but also reduced oxidative stress, as indicated by lower reactive oxygen species levels. Mechanistically, western blotting and mitochondrial membrane potential assays showed that ABCC9 knockdown inhibited the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway and improved mitochondrial function. Notably, these protective effects were diminished by treatment with the PI3K/AKT activator 740Y‑P. These findings collectively suggest that ABCC9 knockdown protects against MH by inhibiting the PI3K/AKT signaling pathway, thereby alleviating mitochondrial dysfunction and reducing apoptosis and oxidative stress, positioning ABCC9 as a potential therapeutic target for MH treatment.