Document Detail

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence.
MedLine Citation:
PMID:  17706954     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Our aim was to examine the possible cross-talk of angiotensin II (Ang II) and aldosterone (Aldo) in the regulation of vascular cell senescence in cultured vascular smooth muscle cells (VSMC). METHODS: VSMC were prepared from thoracic aorta of adult male Sprague-Dawley rats. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) staining and expression of p21, p53, p16, and p27. Oxidative stress was determined by measuring NADPH oxidase activity and superoxide production. Signal transduction was examined by immunoblot analysis with or without RNA interference methods. RESULTS: Persistent Ang II (100 nM) stimulation increased SA-beta-gal-stained VSMC and enhanced expression of p21, p53, p16, p27 and Ki-ras2A. These effects of Ang II were markedly inhibited by treatment with a selective AT(1) receptor blocker, valsartan, but partially attenuated by a mineralocorticoid receptor antagonist, spironolactone. The culture medium of VSMC treated with Ang II (100 nM) showed a time-dependent increase in Aldo concentration, which increased senescent VSMC. Antioxidant, N-acetyl-l-cysteine or superoxide dismutase attenuated Ang II- or Aldo-induced VSMC senescence and Ki-ras2A expression. A lower dose combination of Ang II (100 pM) and Aldo (1 pM) significantly enhanced SA-beta-gal-stained VSMC with increases in expression of p21, p53, p16, p27 and Ki-ras2A, oxidative stress, and activity of transcription factors such as NF-kappaB, AP-1, whereas Ang II or Aldo alone at these doses did not affect these parameters. Ki-ras2A-siRNA treatment attenuated senescent VSMC, expression of p21, p53, p16 and p27, oxidative stress induced by Ang II or a lower dose combination of Ang II and Aldo. CONCLUSION: These results suggest that Ang II and Aldo exert cross-talk in VSMC senescence with involvement of oxidative stress and Ki-ras2A, and could provide a therapeutic benefit for age-related vascular disorders by blockade of both Ang II and Aldo.
Li-Juan Min; Masaki Mogi; Jun Iwanami; Jian-Mei Li; Akiko Sakata; Teppei Fujita; Kana Tsukuda; Masaru Iwai; Masatsugu Horiuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-24
Journal Detail:
Title:  Cardiovascular research     Volume:  76     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2009-03-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  506-16     Citation Subset:  IM    
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Ehime 791-0295, Japan.
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MeSH Terms
Aldosterone / metabolism*,  pharmacology
Angiotensin II / metabolism*,  pharmacology
Aorta, Thoracic / cytology,  metabolism
Cell Aging / physiology*
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Dose-Response Relationship, Drug
Muscle, Smooth, Vascular / cytology*,  metabolism*
Oxidative Stress / physiology
Proto-Oncogene Proteins p21(ras) / metabolism
RNA, Small Interfering / pharmacology
Rats, Sprague-Dawley
Receptor Cross-Talk / physiology*
Renin-Angiotensin System / physiology
Spironolactone / pharmacology
Tetrazoles / pharmacology
Tumor Suppressor Protein p53 / metabolism
Valine / analogs & derivatives,  pharmacology
beta-Galactosidase / metabolism
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/Kras protein, rat; 0/RNA, Small Interfering; 0/Tetrazoles; 0/Tumor Suppressor Protein p53; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 7004-03-7/Valine; EC; EC Proteins p21(ras)

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