Cited by 725Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionCardiovascular and exercise physiology

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Aging and vascular endothelial function in humans

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Seals, Douglas R., Jablonski, Kristen L., Donato, Anthony J.·2011·Clinical Science

DOI 10.1042/cs20100476PMC PMC3482987

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Abstract

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging.

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Authors: Seals, D. R., Jablonski, K. L., & Donato, A. J.
Affiliations: University of Colorado Boulder (US)
ORCID: Seals, Douglas R.
Donato, Anthony J.
Venue: Clinical Science
Publisher: Portland Press Ltd.
Published: 2011-01-18
Volume: 120
Issue: 9
Pages: 357-375
ISSN: 0143-5221 (ISSN-L)
1470-8736
DOI: 10.1042/cs20100476
PMC: PMC3482987
OpenAlex: W1983986440
Cited by: 725
References: 191
Citations by year: 2026: 63 · 2025: 49 · 2024: 45 · 2023: 52 · 2022: 66 · 2021: 58 · 2020: 48 · 2019: 49 · 2018: 49 · 2017: 39 · 2016: 44 · 2015: 46 · 2014: 35 · 2013: 28 · 2012: 40
FWCI: 25.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Clinical Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (AG022241, K01AG029337, AG031141, AG-006537, R01AG031141, AG 029337, F31AG033994, R01AG022241, AG-000279, R37AG013038, R01AG013038, R01AG040297, R01AG006537, AG-013038, AG033994, T32AG000279)
National Center for Research Resources (RR-00051, M01RR000051)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
Keywords: vascular aging, endothelial dysfunction, endothelium-dependent dilation, nitric oxide bioavailability, oxidative stress, superoxide, NADPH oxidase, endothelial nitric oxide synthase, tetrahydrobiopterin, endothelin-1, advanced glycation end products, vascular inflammation, endothelial cell apoptosis, estrogen receptor alpha, menopause, aerobic exercise, dietary factors, vitamin D, cardiovascular risk
MeSH terms: Aging, Cardiovascular Diseases, Endothelium, Vascular, Humans, Inflammation, Nitric Oxide, Vasodilation, Exercise, Oxidative Stress

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Aging and vascular endothelial function in humans

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