Long-term stimulation of angiotensin II induced endothelial senescence and dysfunction.

The role of angiotensin II (Ang II) in hypertension has been clarified, but recent studies show that aging-associated arterial changes and those with hypertension as well as atherosclerosis may have some common pathogenesis. This study aimed to clarify the effects of Ang II on endothelial senescence by establishing a replicative senescence model of human umbilical vein endothelial cells (HUVECs) in vitro. The population-doubling level (PDL) was calculated, PDL5 and PDL25 respectively referred to cells cultured for 2 days and 30 days. Compared with Ang II-treated young PDL5 cells, chronic stimulation of Ang II significantly promoted the senescence-associated β-galactosidase activity and expression of senescence-related genes p16 and p21, slowed down cell growth rate, and decreased expression of longevity-related genes sirtuin1 as well as telomerase activity in senescent PDL25 cells (all P < 0.05). Moreover, expression of pro-inflammatory cytokines and adhesion molecules were up-regulated in Ang II-treated PDL25 cells (all P < 0.05). Ang II-induced senescent progression and inflammation were attenuated by angiotensin receptor blocker valsartan. In young PDL5 cells, Ang II promoted the endothelial viability including cell proliferation, migration, angiogenesis and cell adhesion to monocytes; however, chronic stimulation of Ang II suppressed the cell viability, promoted cell adhesion and apoptosis in senescent PDL25 cells, which could be ameliorated by short-term valsartan, but long-term valsartan had no effects. In addition, Ang II-induced senescent features could be partly recovered if Ang II was stopped at PDL20. These findings suggested that chronic stimulation of Ang II can accelerate the endothelial senescence process which is implicated in aging-related atherosclerosis.