Epigallocatechin-3-gallate exerts protective effect on epithelial function via PI3K/AKT signaling in thrombosis.

Abstract

Venous thrombosis (VT) is one of the most frequent cardiovascular diseases, which seriously endangers people's health. Recently, the protective role of epigallocatechin-3-gallate (EGCG) against multiple cardiovascular diseases has been well studied. Nevertheless, whether EGCG is implicated in the progression of VT is still unclear. Rat models of VT were established by inferior vena cava (IVC) ligation. Histological characterization of the IVC tissues was examined by hematoxylin-eosin (H&E) staining. TUNEL assay was utilized to detect cell apoptosis in IVC tissues. The concentrations of the oxidative stress biomarkers, malondialdehyde (MDA) and superoxide dismutase (SOD), were estimated by corresponding kits. In addition, the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 in rat plasma were estimated by ELISA. Further, the expression levels of apoptosis markers (Bax, Bcl-2, and Cleaved-caspase 3) as well as key molecules p-PI3K and p-AKT in phosphoinositide 3-kinase (PI3K)/AKT signaling pathway were assessed by western blot. Compared to the sham group, the model group showed obvious thrombus formation in IVC tissues, while the EGCG treatment significantly repressed thrombosis. EGCG inhibited cell apoptosis in IVC tissues of VT rat models. The decreased SOD concentration and increased MDA concentration in the plasma of VT rats were reversed by EGCG treatment. Additionally, the elevated levels of TNF-α, IL-6 and IL-8 in the plasma of VT rats can be partially reduced by the treatment of EGCG. Finally, we also found that EGCG reduced the levels of phosphorylated (p)-PI3K and p-AKT in IVC tissues of VT rat models, indicating that the hyperactivation of the PI3K/AKT signaling pathway was inhibited by EGCG. This study proves that EGCG alleviates thrombosis, cell apoptosis, inflammatory response, and oxidative stress injury in VT by inactivating PI3K/AKT signaling pathway.