Red wine polyphenols may preserve endothelial function during aging. Endothelial cell senescence enhances age-related endothelial dysfunction. We investigated whether RWE (red wine extract) prevents oxidative-stress-induced senescence in HUVECs (human umbilical-vein endothelial cells). Senescence was induced by exposing HUVECs to tBHP (t-butylhydroperoxide), and quantified by senescence-associated β-galactosidase staining. RWE (0–50 μg/ml) concentration dependently decreased senescence by maximally 33±7.1%. RWE prevented the senescence-associated increase in p21 protein expression, inhibited tBHP-induced DNA damage of endothelial cells and induced relaxation of PCAs (porcine coronary arteries). Inhibition of SIRT1 (sirtuin 1) by sirtinol partially reversed the effect of RWE on tBHP-induced senescence, whereas both the NOS (nitric oxide synthase) inhibitor L-NMMA (NG-monomethyl-L-arginine) and the COX (cyclo-oxygenase) inhibitor indomethacin fully inhibited it. Furthermore, incubation of HUVECs with RWE increased eNOS (endothelial NOS) and COX-2 mRNA levels as well as phosphorylation of eNOS at Ser1177. RWE protects endothelial cells from tBHP-induced senescence. NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE.
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Research Article|
June 27 2012
Red wine extract protects against oxidative-stress-induced endothelial senescence
Ilse P. G. Botden;
Ilse P. G. Botden
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Hisko Oeseburg;
Hisko Oeseburg
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
†Department of Cardiology, Erasmus University Medical Center, Dr Molewaterplein 50–60, 3015 GE, Rotterdam, The Netherlands
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Matej Durik;
Matej Durik
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Frank P. J. Leijten;
Frank P. J. Leijten
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Leonie C. Van Vark-Van Der Zee;
Leonie C. Van Vark-Van Der Zee
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Usha M. Musterd-Bhaggoe;
Usha M. Musterd-Bhaggoe
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Ingrid M. Garrelds;
Ingrid M. Garrelds
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Ann L. B. Seynhaeve;
Ann L. B. Seynhaeve
‡Laboratory of Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus University Medical Center, Dr Molewaterplein 50–60, 3015 GE, Rotterdam, The Netherlands
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Janneke G. Langendonk;
Janneke G. Langendonk
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Eric J. G. Sijbrands;
Eric J. G. Sijbrands
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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A. H. Jan Danser;
A. H. Jan Danser
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
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Anton J. M. Roks
*Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands
Correspondence: Dr Anton J.M. Roks (email a.roks@erasmusmc.nl).
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Publisher: Portland Press Ltd
Received:
January 03 2012
Revision Received:
April 17 2012
Accepted:
May 08 2012
Accepted Manuscript online:
May 08 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 123 (8): 499–507.
Article history
Received:
January 03 2012
Revision Received:
April 17 2012
Accepted:
May 08 2012
Accepted Manuscript online:
May 08 2012
Citation
Ilse P. G. Botden, Hisko Oeseburg, Matej Durik, Frank P. J. Leijten, Leonie C. Van Vark-Van Der Zee, Usha M. Musterd-Bhaggoe, Ingrid M. Garrelds, Ann L. B. Seynhaeve, Janneke G. Langendonk, Eric J. G. Sijbrands, A. H. Jan Danser, Anton J. M. Roks; Red wine extract protects against oxidative-stress-induced endothelial senescence. Clin Sci (Lond) 1 October 2012; 123 (8): 499–507. doi: https://doi.org/10.1042/CS20110679
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