Knockdown of LTBP4 alleviates OGD/R-induced cardiomyocyte apoptosis and mitochondrial dysfunction, and attenuates the TGF-β signaling pathway

Background: Heart failure (HF) is a prevalent cardiovascular condition that signifi-cantly compromises patient health and survival. Latent transforming growth factor-beta binding protein 4 (LTBP4), an extracellular matrix protein abundantly expressed in the heart, has been implicated in various pathological processes. But, its specific role in HF pathogenesis is insufficiently characterized. Methods: We evaluated protein expression through Western blotting, assessed cell viability through the Cell Counting Kit-8 (CCK-8) assay, and quantified apoptosis by flow cytometry. Additionally, oxidative stress and mitochondrial function were examined by measuring reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using commercial kits, while mitochondrial membrane potential (MMP) was inspected via JC-1 staining. Results: The findings revealed a marked upregulation of LTBP4 expression in oxygen-glucose deprivation/reperfusion (OGD/R). This elevation in LTBP4 coincided with a significant increase in apoptosis, mitochondrial dysfunction, and activation of the transforming growth factor-β (TGF-β) signaling pathway. Notably, silencing LTBP4 effectively mitigated these pathological changes, as evidenced by reduced apoptotic rates, decreased ROS accumulation, preserved ATP production, stabilized MMP, and suppressed TGF-β signaling activity. Conclusions: Taken together, these results provide evidence that LTBP4 knockdown confers protective effects against OGD/R-induced cardiac damage by alleviating apoptosis and mitochondrial dysfunction while concurrently attenuating TGF-β pathway activation, hinting that LTBP4 may represent a helpful therapeutic target in the amelioration of HF.

Heart failure; LTBP4; OGD/R; Mitochondrial dysfunction

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