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Total flavonoids from the Carya cathayensis Sarg. leaves inhibit HUVEC senescence through the miR-34a/SIRT1 pathway
Yan Guo1, Liwan Xing1, Nipi Chen1
1College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
Insights
Total flavonoids (TFs) inhibit endothelial cell senescence, a key factor in vascular aging and cardiovascular disease. This effect is mediated by the miR-34a/Sirtuin1 pathway, offering potential therapeutic insights.
Area of Science:
- Vascular Biology
- Cellular Senescence
- Molecular Mechanisms
Background:
- Aging is linked to vascular dysfunction, with endothelial cell senescence being a major contributor to cardiovascular diseases.
- Advanced age is a nonmodifiable risk factor for cardiovascular conditions.
Purpose of the Study:
- To investigate the impact of total flavonoids (TFs) on human umbilical vein endothelial cell (HUVEC) senescence.
- To elucidate the underlying molecular mechanisms involving the miR-34a/SIRT1 pathway.
Main Methods:
- A HUVEC senescence model was induced using angiotensin II.
- Senescence markers (SA-β-gal, p53, p21, cell cycle distribution) were assessed.
- Quantitative PCR and Western blot analyzed miR-34a and SIRT1 expression, with and without TF and miR-34a inhibitor treatments.
Main Results:
- TFs reduced SA-β-gal positive cells and G0/G1 arrest, increasing S phase.
- TFs decreased miR-34a expression and increased SIRT1 expression.
- Co-treatment with TFs and a miR-34a inhibitor further reduced SA-β-gal and miR-34a, while increasing SIRT1.
Conclusions:
- Total flavonoids effectively inhibit HUVEC senescence.
- The anti-senescence mechanism involves the regulation of the miR-34a/Sirtuin1 pathway.
Abstract:
Aging shows a significant relationship with changed vascular structure and function, and advancing age is a major nonmodifiable risk factor in the occurrence of cardiovascular diseases. The senescence of endothelial cells is one of the hallmarks of vascular aging and can induce vascular dysfunction. This study aimed to investigate the effect of total flavonoids (TFs) on human umbilical vein endothelial cells (HUVEC) senescence and identify the potential mechanisms involved. A HUVEC senescence model was induced by angiotensin II. The senescence markers, including senescence-associated β-galactosidase (SA-β-gal), p53, p21, and stagnate G0/G1, were measured. The effects of TFs on miR-34/ SIRT1 were examined by quantitative polymerase chain reaction analysis and Western blot analysis. TFs decreased the percentage of SA-β-gal-positive cells and resulted in G0/G1 cell cycle arrest, while the percentage of cells in the S phase increased. Furthermore, TFs reduced miR-34a expression and increased the expression of SIRT1. After treatment with TFs and a miR-34a inhibitor, the percentage of SA-β-gal-positive cells and the expression of miR-34a decreased, and the expression of SIRT1 increased. The TFs inhibited HUVEC senescence, and the mechanism was related to the miR-34a/Sirtuin1 pathway.
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