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Nuclear Factor-κB Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight/Obese Middle-Aged and Older Humans
Open accessAbstract
Background— We tested the hypothesis that nuclear factor-κB (NF-κB) activity contributes to vascular endothelial dysfunction with aging and obesity in humans. Methods and Results— We conducted a randomized, double-blind, placebo-controlled crossover study in 14 nondiabetic overweight or obese (body mass index ≥25 kg/m 2 ) middle-aged and older (age 52 to 68 years) adults. Salsalate (nonacetylated salicylate, 4500 mg/d), a compound that inhibits NF-κB activity, or placebo was administered for 4-day periods. Plasma salicylate concentrations reached the midtherapeutic range (21.8±1.1 mg/100 mL, P ≤0.0001 versus placebo) by day 4 of salsalate treatment. Salsalate increased expression of the inhibitor of NF-κB and reduced total and nuclear expression of NF-κB in endothelial cells obtained from the subjects (all P <0.05). Salsalate increased brachial artery flow-mediated dilation by 74% (from 4.0±0.4% to 6.6±0.5%, P <0.001) but did not affect endothelium-independent dilation ( P =0.83). The change in brachial artery flow-mediated dilation with salsalate was inversely related to baseline flow-mediated dilation ( r =−0.77, P <0.01). Infusion of vitamin C increased brachial artery flow-mediated dilation during placebo ( P <0.001) but not after salsalate ( P =0.23). Salsalate reduced nitrotyrosine ( P =0.06) and expression of NADPH oxidase p47 phox ( P <0.05) in endothelial cells obtained from the subjects but did not influence circulating or endothelial cell inflammatory proteins. Conclusions— Our findings provide the first direct evidence that NF-κB, in part via stimulation of oxidative stress, plays an important role in mediating vascular endothelial dysfunction in overweight and obese middle-aged and older humans.
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“and is a key mechanism mediating age-related arterial dysfunction (34, 45, 149, 162)”
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Pearson, T. A., Mensah, G. A., Alexander, R. W., Anderson, J. L., Cannon, R. O., Criqui, M., Fadl, Y. Y., Fortmann, S. P., Hong, Y., Myers, G. L., et al. (2003) · Circulation · doi:10.1161/01.cir.0000052939.59093.45 · Cited by 6,401
PearsonT, A., MensahG, A., & AlexanderR, W. (2003) · Journal of Cardiopulmonary Rehabilitation · doi:10.1097/00008483-200305000-00016 · Cited by 2,937
Lakatta, E. G., & Levy, D. (2003) · Circulation · doi:10.1161/01.cir.0000048892.83521.58 · Cited by 2,244
Inhibition of NF-κB by Sodium Salicylate and Aspirin
Kopp, E. B., & Ghosh, S. (1994) · Science · doi:10.1126/science.8052854 · Cited by 1,744
Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118709 · Cited by 1,687
The effect of age on the association between body-mass index and mortality
Stevens, J., Cai, J., Pamuk, E. R., Williamson, D. F., Thun, M. J., & Wood, J. L. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801013380101 · Cited by 1,611
The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β
Yin, M.-J., Yamamoto, Y., & Gaynor, R. B. (1998) · Nature · doi:10.1038/23948 · Cited by 1,596
Keaney, J. F., Larson, M. G., Vasan, R. S., Wilson, P. W. F., Lipinska, I., Corey, D., Massaro, J. M., Sutherland, P., Vita, J. A., & Benjamin, E. J. (2003) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000058402.34138.11 · Cited by 1,304
DeSouza, C. A., Shapiro, L. F., Clevenger, C. M., Dinenno, F. A., Monahan, K. D., Tanaka, H., & Seals, D. R. (2000) · Circulation · doi:10.1161/01.cir.102.12.1351 · Cited by 896
Self-citationActivated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion.
Brand, K., Page, S., Rogler, G., Bartsch, A., Brandl, R., Knuechel, R., Page, M., Kaltschmidt, C., Baeuerle, P. A., & Neumeier, D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118598 · Cited by 799
Awtry, E. H., & Loscalzo, J. (2000) · Circulation · doi:10.1161/01.cir.101.10.1206 · Cited by 691
Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes
Hundal, R. S., Petersen, K. F., Mayerson, A. B., Randhawa, P. S., Inzucchi, S. E., Shoelson, S. E., & Shulman, G. I. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14955 · Cited by 627
Hajra, L., Evans, A. I., Chen, M., Hyduk, S. J., Collins, T., & Cybulsky, M. I. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.9052 · Cited by 587
Nuclear Factor κB Signaling in Atherogenesis
de Winther, M. P. J., Kanters, E., Kraal, G., & Hofker, M. H. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000160340.72641.87 · Cited by 586
Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function
Csiszár, A., Ungvari, Z. I., Edwards, J. G., Kaminski, P. M., Wolin, M. S., Koller, Á., & Kaley, G. (2002) · Circulation Research · doi:10.1161/01.res.0000020401.61826.ea · Cited by 569
Direct Evidence of Endothelial Oxidative Stress With Aging in Humans
Donato, A. J., Eskurza, I., Silver, A., Levy, A., Pierce, G. L., Gates, P. E., & Seals, D. R. (2007) · Circulation Research · doi:10.1161/01.res.0000269183.13937.e8 · Cited by 566
Self-citationMechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes
Hundal, R. S., Petersen, K. F., Mayerson, A. B., Randhawa, P. S., Inzucchi, S., Shoelson, S. E., & Shulman, G. I. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214955 · Cited by 557
The molecular inflammatory process in aging
Chung, H. Y., Sung, B., Jung, K. J., Zou, Y., & Yu, B. P. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.572 · Cited by 437
NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial activation.
Read, M. A., Whitley, M. Z., Williams, A. J., & Collins, T. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.503 · Cited by 404
NF-κB Regulates Phagocytic NADPH Oxidase by Inducing the Expression of gp91
Anrather, J., Racchumi, G., & Iadecola, C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m506172200 · Cited by 397
Ungvari, Z. I., Orosz, Z. Z., Labinskyy, N., Rivera, A., Xiangmin, Z., Smith, K. E., & Csiszár, A. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01346.2006 · Cited by 352
Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults
Fleischman, A., Shoelson, S. E., Bernier, R., & Goldfine, A. B. (2008) · Diabetes Care · doi:10.2337/dc07-1338 · Cited by 346
Eskurza, I., Monahan, K. D., Robinson, J. A., & Seals, D. R. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2003.057042 · Cited by 341
Self-citationObesity and Body Fat Distribution Induce Endothelial Dysfunction by Oxidative Stress
Perticone, F., Ceravolo, R., Candigliota, M., Ventura, G., Iacopino, S., Sinopoli, F., & Mattioli, P. L. (2001) · Diabetes · doi:10.2337/diabetes.50.1.159 · Cited by 336
Pierce, J. W., Read, M. A., Ding, H. T., Luscinskas, F. W., & Collins, T. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.10.3961 · Cited by 301
Csiszár, A., Smith, K. E., Labinskyy, N., Orosz, Z. Z., Rivera, A., & Ungvari, Z. I. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00340.2006 · Cited by 275
Aging‐induced proinflammatory shift in cytokine expression profile in rat coronary arteries
Csiszár, A., Ungvari, Z. I., Koller, Á., Edwards, J. G., & Kaley, G. (2003) · The FASEB Journal · doi:10.1096/fj.02-1049fje · Cited by 266
Donato, A. J., Black, A. D., Jablonski, K. L., Gano, L. B., & Seals, D. R. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00438.x · Cited by 237
Self-citationRegulation of Bone Morphogenetic Protein-2 Expression in Endothelial Cells
Csiszár, A., Smith, K. E., Koller, Á., Kaley, G., Edwards, J. G., & Ungvari, Z. I. (2005) · Circulation · doi:10.1161/01.cir.0000164201.40634.1d · Cited by 218
Silver, A., Beske, S. D., Christou, D. D., Donato, A. J., Moreau, K. L., Eskurza, I., Gates, P. E., & Seals, D. R. (2007) · Circulation · doi:10.1161/circulationaha.106.657486 · Cited by 190
Self-citationPreliminary evidence that DEXA provides an accurate assessment of body composition
Kohrt, W. M. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.1.372 · Cited by 186
Eskurza, I., Myerburgh, L. A., Kahn, Z. D., & Seals, D. R. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.092734 · Cited by 175
Self-citationChristou, D. D., Gentile, C. L., DeSouza, C. A., Seals, D. R., & Gates, P. E. (2005) · Circulation · doi:10.1161/01.cir.0000161818.28974.1a · Cited by 131
Self-citationEndothelial Cell Activation in Patients With Decompensated Heart Failure
Colombo, P. C., Banchs, J. E., Celaj, S., Talreja, A., Lachmann, J. S., Malla, S., Dubois, N. B., Ashton, A. W., Latif, F., Jorde, U. P., et al. (2004) · Circulation · doi:10.1161/01.cir.0000151611.89232.3b · Cited by 122
Regulation of NADPH oxidase subunit p22phoxby NF-kB in human aortic smooth muscle cells
Manea, A., Manea, S., Gafencu, A. V., & Raicu, M. (2007) · Archives of Physiology and Biochemistry · doi:10.1080/13813450701531235 · Cited by 114
Gates, P. E., Boucher, M. L., Silver, A., Monahan, K. D., & Seals, D. R. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00660.2006 · Cited by 107
Self-citationWu, K. K. (2000) · Circulation · doi:10.1161/01.cir.102.17.2022 · Cited by 102
Eskurza, I., Kahn, Z. D., & Seals, D. R. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2005.102566 · Cited by 99
Self-citationSellers, M., & Stallone, J. N. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01318.2007 · Cited by 86
Csiszár, A., Smith, K. E., Labinskyy, N., Orosz, Z. Z., Rivera, A., & Ungvari, Z. I. (2007) · The FASEB Journal · doi:10.1096/fasebj.21.5.a450-a · Cited by 84
Colombo, P. C., Ashton, A. W., Celaj, S., Talreja, A., Banchs, J. E., Dubois, N. B., Marinaccio, M., Malla, S., Lachmann, J. S., Ware, J. A., et al. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00680.2001 · Cited by 79
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Zou, Y., Yoon, S. Y., Jung, K. J., Kim, C. H., Son, T. G., Kim, M.-S., Kim, Y. J., Lee, J., Yu, B. P., & Chung, H. Y. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.3.232 · Cited by 69
Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins
Cryer, B., Goldschmiedt, M., Redfern, J. S., & Feldman, M. L. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90465-d · Cited by 60
Gupta, S. K., Johnson, R. M., Saha, C., Mather, K. J., Greenwald, M., Waltz, J., Rehman, J., & Dubé, M. P. (2008) · AIDS · doi:10.1097/qad.0b013e3282f470d2 · Cited by 33
Secretory products from human adipocytes impair endothelial function via nuclear factor κB
Kralisch, S., Sommer, G., Stangl, V., Köhler, U., Kratzsch, J., Stepan, H., Faber, R., Schubert, A., Lössner, U., Vietzke, A., et al. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.05.016 · Cited by 32
Availability of salicylate from salsalate and aspirin
Dromgoole, S. H., Cassell, S., Furst, D. E., & Paulus, H. E. (1983) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1983.211 · Cited by 19
Assessment of salsalate, a nonacetylated salicylate, in the treatment of patients with arthritis
Atkinson, M. H. (1995) · Clinical Therapeutics · doi:10.1016/0149-2918(95)80061-1 · Cited by 17
Metabolism of Salsalate in Normal Subjects
Dromgoole, S. H., Furst, D. E., & Paulus, H. E. (1984) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600731147 · Cited by 15
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Metadata
- Authors
- Pierce, G. L., Lesniewski, L. A., Lawson, B. R., Beske, S. D., & Seals, D. R.
- Affiliations
- University of Colorado Boulder (US)
- Venue
- Circulation
- Published
- 2009-03-10
- Volume
- 119
- Issue
- 9
- Pages
- 1284-1292
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2810548
- OpenAlex
- W2160375807
- Cited by
- 262
- References
- 47
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 10 · 2023: 16 · 2022: 15 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 17 · 2017: 11 · 2016: 12 · 2015: 19 · 2014: 20 · 2013: 17 · 2012: 20
- FWCI
- 14.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG022241, AG-006537, R01AG022241, AG-000279, R37AG013038, R01AG013038, AG015897, R01AG006537, R01AG015897, AG-013038, T32AG000279)
- National Center for Research Resources (RR-00051, M01RR000051)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- NF-κB activation, endothelial dysfunction, oxidative stress, obesity, aging, salsalate, flow-mediated dilation, nitrotyrosine, vitamin C, endothelial cells, middle-aged and older adults
- MeSH terms
- NF-KappaB Inhibitor alpha, Administration, Oral, Aged, Aging, Anti-Inflammatory Agents, Non-Steroidal, Endothelium, Vascular, Female, Humans, Male, Middle Aged, Obesity, Salicylates, Tyrosine, Vasodilation, Body Mass Index, Cytokines, NF-kappa B, Oxidative Stress, Cross-Over Studies, NADPH Oxidases, I-kappa B Proteins, Overweight, Cyclooxygenase 1, Cyclooxygenase 2
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