Angiotensin II induces endothelial cell senescence via the activation of mitogen-activated protein kinases.
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 beta-galactosidase (SA-beta-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.
Shan
Haiyan
H
Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Bai
XiaoJuan
X
Chen
XiangMei
X
D000804:Angiotensin II / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D046529:Microscopy, Electron, Transmission; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014470:Umbilical Cord / Q000187:drug effects / Q000201:enzymology
D019253:Proto-Oncogene Proteins c-bcl-2; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases