Angiotensin II induces endothelial cell senescence via the activation of mitogen‐activated protein kinases

Abstract Vascular endothelial cells have a finite cell lifespan and eventually enter an irreversible growth arrest, cellular senescence. The functional changes associated with cellular senescence are thought to contribute to human aging and age‐related cardiovascular disorders, for example, atherosclerosis. Angiotensin II (Ang II), a principal effector of the renin‐angiotensin system (RAS), an important signaling molecule involved in atherogenic stimuli, is known to promote aging and cellular senescence. In the present study, induction of Ang II promoted a growth arrest with phenotypic characteristics of cell senescence, such as enlarged cell shapes, increased senescence‐associated ß‐galactosidase (SA‐ß‐gal) positive staining cells, and depressed cell proliferation. Ang II drastically decreased the expression level of Bcl‐2, in part via the activation of extracellular signal‐regulated kinase (ERK). Our results suggest that Ang II can induce HUVEC senescence; one of its molecular mechanisms is a probability that the mitogen‐activated protein kinase (MAPK) signal pathway is involved in the process of pathological and physiological senescence of endothelial cells as well as vascular aging. Copyright © 2008 John Wiley & Sons, Ltd.