Key result
Sirt6 overexpression attenuates CVB3-induced EndMT and apoptosis by restoring autophagy and reducing oxidative stress.
Why the study?
Sirt6 plays a critical role in cardiovascular pathophysiology, but its involvement in viral myocarditis remains poorly understood.
Does Sirt6 regulate Coxsackievirus B3-induced endothelial-to-mesenchymal transition in cardiac endothelial cells?
Does Sirt6 regulate Coxsackievirus B3-induced endothelial-to-mesenchymal transition in cardiac endothelial cells?
Answers are grounded in this paper and cite their sources.
This basic science study provides mechanistic evidence that Sirt6 protects cardiac endothelial cells from Coxsackievirus B3-induced injury, suggesting a potential therapeutic target for viral myocarditis.
OBJECTIVE: Sirtuin 6 (Sirt6) plays a critical role in cardiovascular pathophysiology, yet its involvement in viral myocarditis (VMC) remains poorly understood. This study aimed to investigate the role of Sirt6 in coxsackievirus B3 (CVB3)-induced endothelial-to-mesenchymal transition (EndMT) and its underlying molecular mechanisms. METHODS: A model of CVB3-infected mouse cardiac endothelial cells (MCECs) was established. EndMT markers and Sirt6 expression were detected by WB/IF and qRT-PCR. Lentivirus-mediated Sirt6 knockdown or overexpression was performed to examine its impact on EndMT. Apoptosis and apoptosis-related proteins were analyzed by flow cytometry and WB. Proteomic analysis was further conducted on Sirt6-knockdown MCECs and their controls. Based on the results, oxidative stress and autophagy were assessed in CVB3-induced EndMT, and the influence of altered Sirt6 expression on these indicators was evaluated. RESULTS: Sirt6 expression was significantly downregulated in CVB3-induced EndMT. Sirt6 knockdown promoted EndMT, as manifested by decreased vascular endothelial cadherin (VE-cad) and increased α-smooth muscle actin (α-SMA) expression. It also exacerbated apoptosis, accompanied by upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2, and an increase in Caspase-3 expression. Sirt6 overexpression partially reversed these changes. Proteomic analysis indicated that Sirt6 was involved in inflammatory signaling, apoptotic cascades, redox homeostasis, and metabolic pathways. CVB3 infection markedly elevated intracellular oxidative stress (increased ROS and MDA levels, decreased SOD activity) and suppressed autophagy (reduced LC3B-II and Beclin-1, elevated p62). These CVB3‑induced effects were aggravated by Sirt6 knockdown but attenuated by Sirt6 overexpression. CONCLUSION: This study reveals that Sirt6 inhibits CVB3-induced EndMT by regulating oxidative stress and autophagy. These findings provide experimental evidence for elucidating the pathological mechanisms of VMC and suggest Sirt6 as a potential therapeutic target.
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Yang et al. (2025) studied Coxsackievirus B3-induced endothelial-to-mesenchymal transition (EndMT) in viral myocarditis (in vitro model). Sirt6 genetic manipulation (knockdown and overexpression) vs. Negative control lentiviral vectors (sh-NC, oe-NC) was evaluated on Endothelial-to-mesenchymal transition (EndMT) markers (VE-cad and alpha-SMA) and cellular apoptosis (p=<0.05). Sirt6 overexpression significantly attenuated CVB3-induced endothelial-to-mesenchymal transition and apoptosis by decreasing oxidative stress and restoring autophagy.
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