ET1 acts as a potential plasma biomarker and therapeutic target in deep venous thrombosis rat model

TL;DR

This study explores ET-1 as a potential blood marker and treatment target for deep venous thrombosis in rats.

Contribution

The study identifies ET-1 as a novel early diagnostic biomarker and therapeutic target for DVT in a rat model.

Findings

ET-1 overexpression in HUVECs impairs cell proliferation and migration while increasing apoptosis.

ET-1 upregulates coagulation factor VII and inhibits antioxidant signaling proteins like NQO1 and Nrf-2.

ET-1 inhibition with BQ123 reduces coagulation factor VII and mitigates DVT effects in a rat model.

Abstract

Deep venous thrombosis (DVT) is the third leading cause of death in cardiovascular disease, following heart attacks and strokes. Early diagnosis and intervention are crucial for effective DVT therapy. We aim to investigate whether endothelin-1 (ET-1) could serve as an early diagnostic marker or a potential therapeutic target in a DVT rat model. CCK8 assay, invasion assay, and flow cytometry were used to detect the proliferation, migration and apoptosis of HUVECs, respectively. Elisa assay was used to detect ET-1 and coagulation factor VII in cell supernatant and rat?s plasma. Western blot was used to detect antioxidant signaling protein. Inferior vena cava stenosis was used to construct the DVT rat model. Lentivirus mediated overexpression of ET-1 in HUVECs impaired the cell proliferation and migration, increased cell apoptosis, inhibited the antioxidant signaling pathway proteins expression (e.g., NQO1, GCLC, Nrf-2), and upregulated coagulation factor VII. Furthermore, overexpression of ET-1 further impaired antioxidant signaling pathway protein in response to H2O2 treatment. However, lentivirus mediated ET-1 knockdown and BQ123 (an ET-1 inhibitor), showed the opposite results with ET-1 overexpression. We then established a DVT rat model by inferior vena cava stenosis. The stenosis induced early expression of ET-1 and coagulation factor VII in plasma at day 1 and restore their level at day 10. BQ123 could downregulate the coagulation factor VII to ameliorate the stenosis effects. Our findings suggest that ET-1 might serve as an early diagnostic marker for DVT rat model and a potential therapeutic target for treating DVT.

The online version contains supplementary material available at 10.1007/s11239-024-02981-4.

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