Involvement of Flavonoids from the Leaves of Sarg. in Sirtuin 1 Expression in HUVEC Senescence.

Atherosclerosis is the commonest cause of death in the world and one of the most important processes that occurs with increasing age because it is accompanied by progressive endothelial dysfunction. Recent studies demonstrated that Sirtuin 1 (SIRT1) might potentially affect cell senescence. However, the effect of SIRT1 on the regulation of human umbilical vein endothelial cell (HUVEC) senescence with total flavonoids (TFs) has not been addressed previously. This study investigated how SIRT1 functions in the process of HUVEC senescence when TFs are present and identified the potential molecular mechanisms involved. Using a model of HUVEC senescence induced by angiotensin II, TFs pretreatment reduced the percentage of senescence-associated -galactosidase (SA--gal) cells and p53 mRNA expression. The level of SIRT1 protein and E2F1 decreased during HUVEC senescence and could be partially recovered when cells were coincubated with TFs, while the levels of proteins p53 and p21 increased during cell senescence and diminished in response to the TFs treatment. When coincubated with 20 mM nicotinamide, the results with SA--gal-positive cells and the expression of SIRT1, E2F1, p53, and p21 were contrary to that obtained with only TFs pretreatment. The data indicate that the TFs exert their effect on HUVEC senescence through SIRT1.