The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Induction of Endothelial Nitric Oxide Synthase, SIRT1, and Catalase by Statins Inhibits Endothelial Senescence Through the Akt Pathway
Abstract
Objective— Statins (3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors) have pleiotropic vascular protective effects besides cholesterol lowering. Recently, experimental and clinical studies have indicated that senescence of endothelial cells is involved in endothelial dysfunction and atherogenesis. Therefore, the present study was performed to determine whether statins would reduce endothelial senescence and to clarify the molecular mechanisms underlying the antisenescent property of statins. Methods and Results— Senescent human umbilical vein endothelial cells were induced by hydrogen peroxide (H 2 O 2 ), as judged by senescence-associated β-galactosidase assay and cell morphological appearance. Atorvastatin, pravastatin, and pitavastatin inhibited the oxidative stress induced-endothelial senescence. These statins phosphorylated Akt at Ser473 and subsequently led to increased expression of endothelial nitric oxide synthase (eNOS), SIRT1, and catalase. Treatment with LY294002 or Akt short interfering RNA decreased the eNOS activation, SIRT1 expression, and antisenescent property of atorvastatin. Moreover, in streptozotocin-diabetic mice, administration of pitavastatin increased eNOS, SIRT1, and catalase expression and decreased endothelial senescence, but levels remained unaltered in Sirt1 knockout mice. Conclusion— Our results indicate that treatment with statins inhibits endothelial senescence and that enhancement of SIRT1 plays a critical role in prevention of endothelial senescence through the Akt pathway, a direct target of statins.
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
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Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047
SIRT1 Controls Endothelial Angiogenic Functions During Vascular Growth
Potente, M., Ghaeni, L., Baldessari, D., Mostoslavsky, R., Rossig, L., Dequiedt, F., Haendeler, J., Mione, M., Dejana, E., Alt, F. W., et al. (2007) · Genes & Development · doi:10.1101/gad.435107 · Cited by 608
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Sirtuins, a promising target in slowing down the ageing process
Grabowska, W., Sikora, E., & Bielak-Zmijewska, A. (2017) · Biogerontology · doi:10.1007/s10522-017-9685-9 · Cited by 470
SIRT‐1 and vascular endothelial dysfunction with ageing in mice and humans
Donato, A. J., Magerko, K. A., Lawson, B. R., Durrant, J. R., Lesniewski, L. A., & Seals, D. R. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.211219 · Cited by 271
Disturbed Flow Promotes Endothelial Senescence via a p53-Dependent Pathway
Warboys, C. M., de Luca, A., Amini, N., Luong, L., Duckles, H., Hsiao, S., White, A., Biswas, S., Khamis, R., Chong, C. K., et al. (2014) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.114.303415 · Cited by 227
Zarzuelo, M. J., López-Sepúlveda, R., Sánchez, M., Romero, M., Gómez-Guzmán, M., Ungvary, Z., Pérez-Vizcaíno, F., Jiménez, R., & Duarte, J. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.02.015 · Cited by 202
Cell senescence in liver diseases: pathological mechanism and theranostic opportunity
Sanfeliu-Redondo, D., Gibert-Ramos, A., & Gracia-Sancho, J. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00913-4 · Cited by 117
Metadata
- Authors
- Ota, H., Eto, M., Kano, M. R., Kahyo, T., Setou, M., Ogawa, S., Iijima, K., Akishita, M., & Ouchi, Y.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2010-11
- Volume
- 30
- Issue
- 11
- Pages
- 2205-2211
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2121141378
- Cited by
- 218
- References
- 6
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Induction of Endothelial Nitric Oxide Synthase, SIRT1, and Catalase by Statins Inhibits Endothelial Senescence Through the Akt Pathway. https://app.cochat.ai/papers/10.1161/atvbaha.110.210500
- The paper
- Ota, H., Eto, M., Kano, M. R., Kahyo, T., Setou, M., Ogawa, S., Iijima, K., Akishita, M., & Ouchi, Y. (2010). Induction of Endothelial Nitric Oxide Synthase, SIRT1, and Catalase by Statins Inhibits Endothelial Senescence Through the Akt Pathway. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/atvbaha.110.210500
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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