Cited by 563Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionTelomeres, Telomerase, and Senescence

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Endothelial aging

BRANDES, R, FLEMING, I, BUSSE, R·2005·Cardiovascular Research

DOI 10.1016/j.cardiores.2004.12.027

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Abstract

Aging is considered to be the major risk factor for the development of atherosclerosis and, therefore, for coronary artery disease. Apart from age-associated remodeling of the vascular wall, which includes luminal enlargement, intimal and medial thickening, and increased vascular stiffness, endothelial function declines with age. This is most obvious from the attenuation of endothelium-dependent dilator responses, which is a consequence of the alteration in the expression and/or activity of the endothelial NO synthase, upregulation of the inducible NO synthase, and increased formation of reactive oxygen species. Aging is also associated with a reduction in the regenerative capacity of the endothelium and endothelial senescence, which is characterized by an increased rate of endothelial cell apoptosis.

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BackgroundMethod
Endothelial Cell Senescence and Age-Related Vascular Diseases
Tian, X., & Yang, L. (2014) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2014.08.001 · Cited by 139
“Inflammaging” as a druggable target: a senescence-associated secretory phenotype-centered view of type 2 diabetes
Prattichizzo, F., De Nigris, V., La Sala, L., Procopio, A. D., Olivieri, F., & Ceriello, A. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1810327 · Cited by 129
“There is growing epidemiological evidence that a state of mild inflammation is associated with and predicts several age-related diseases (ARDs), including type 2 diabetes mellitus (T2DM) and its complications (e.g., cardiac death) [3–5].”
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Ageing and microvasculature
Scioli, M. G., Bielli, A., Arcuri, G., Ferlosio, A., & Orlandi, A. (2014) · Vascular Cell · doi:10.1186/2045-824x-6-19 · Cited by 132
“It has been demonstrated that endothelin-1 and angiotensin II (potent vasoconstrictors) pathways are involved in age-related endothelial oxidative stress [18].”
Separating vascular and neuronal effects of age on fMRI BOLD signals
Tsvetanov, K. A., Henson, R. N., & Rowe, J. B. (2020) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2019.0631 · Cited by 136
“Likely causes for CVR changes are arterial stiffening [83] and compromised endothelial function in blood vessels [84], which lead to a decreased vascular response to match metabolic demands.”
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Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging
Hwang, H. J., Kim, N., Herman, A. B., Gorospe, M., & Lee, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710135 · Cited by 138
Positive crosstalk between arginase‐II and S6K1 in vascular endothelial inflammation and aging
Yepuri, G., Velagapudi, S., Xiong, Y., Rajapakse, A. G., Montani, J., Ming, X., & Yang, Z. (2012) · Aging Cell · doi:10.1111/acel.12001 · Cited by 129
Lipid Raft Redox Signaling: Molecular Mechanisms in Health and Disease
Jin, S., Zhou, F., Katirai, F., & Li, P. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3619 · Cited by 134
“It is now widely accepted that ROS and, in particular, H2O2 are involved in all types of signaling, including synaptic signaling (364), paracrine signaling (319, 448), autocrine signaling (43), and intracellular signaling (176), as a mediator or modulator of signal transduction.”
Functional and morphological characteristics of the retinal and choroidal vasculature
Yu, D., Yu, P. K., Cringle, S. J., Kang, M. H., & Su, E. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.02.001 · Cited by 126
The Impact of Aging on Cardio and Cerebrovascular Diseases
Izzo, C., Carrizzo, A., Alfano, A., Virtuoso, N., Capunzo, M., Calabrese, M., Simone, E. D., Sciarretta, S., Frati, G., Oliveti, M., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020481 · Cited by 134
“Interestingly, both eNOS and iNOS are subject to uncoupling in absence of the same substrates [129].”
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Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations
Cobley, J. N., McHardy, H., Morton, J. P., Nikolaidis, M. G., & Close, G. L. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.03.018 · Cited by 118
MicroRNAs in vascular aging and atherosclerosis
Menghini, R., Stöhr, R., & Federici, M. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.03.005 · Cited by 120
Satellite cells in ageing: use it or lose it
Chen, W., Datzkiw, D., & Rudnicki, M. A. (2020) · Open Biology · doi:10.1098/rsob.200048 · Cited by 122
New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach
Liu, Y., Weng, W., Gao, R., & Liu, Y. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4598167 · Cited by 118
“It is also associated with coronary atherosclerotic heart disease [149, 150].”
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Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness
Soucy, K. G., Ryoo, S., Benjo, A., Lim, H. K., Gupta, G., Sohi, J. S., Elser, J., Aon, M. A., Nyhan, D., Shoukas, A. A., et al. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00138.2006 · Cited by 135
“Furthermore, these disorders share various features with aging (3, 31, 47), potentially implicating Akt as a component in these vascular disease processes.”
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Age‐Related Alterations in Reactivity of Cerebral Arterioles: Role of Oxidative Stress
Mayhan, W. G., Arrick, D. M., Sharpe, G. M., & Sun, H. (2008) · Microcirculation · doi:10.1080/10739680701641421 · Cited by 112
Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis
Barton, M. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0860-y · Cited by 109
“An interesting study in the longest living rodent, which has a life expectancy of up to 26 years compared with 3 to 4 years in other rodents, found that the vasculature of this particular animal expresses much higher amounts of antioxidant enzymes such as SOD [36], suggesting that cellular (but not dietary) antioxidan…”
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Impaired flow-mediated dilation with age is not explained by l -arginine bioavailability or endothelial asymmetric dimethylarginine protein expression
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
“Several mechanisms are thought to contribute to impaired vascular endothelial function, but reduced bioavailability of nitric oxide (NO) has emerged as a primary factor in older adults (5, 35, 36).”
Perioperative Care for the Older Outpatient Undergoing Ambulatory Surgery
White, P. F., White, L. M., Monk, T. G., Jakobsson, J., Raeder, J. C., Mulroy, M. F., Bertini, L., Torri, G., Solca, M., Pittoni, G. M., et al. (2012) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e31824f19b8 · Cited by 107
“progressive reduction in nitric oxide production with aging also contributes to vascular stiffening.(13) As the aging heart pumps against an increased afterload, the left ventricular wall thickens, leading to ventricular hypertrophy.”
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Vascular endothelium–targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model
Sun, S., Qin, W., Tang, X., Meng, Y., Hu, W., Zhang, S., Qian, M., Liu, Z., Cao, X., Pang, Q., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay5556 · Cited by 108
Cyclin-Dependent Kinase 5–Mediated Hyperphosphorylation of Sirtuin-1 Contributes to the Development of Endothelial Senescence and Atherosclerosis
Bai, B., Liang, Y. Q., Xu, C., Lee, M. Y. K., Xu, A., Wu, D., Vanhoutte, P. M., & Wang, Y. (2012) · Circulation · doi:10.1161/circulationaha.112.118778 · Cited by 105
Vascular ageing: Underlying mechanisms and clinical implications
Laina, A., Stellos, K., & Stamatelopoulos, K. S. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.06.007 · Cited by 106
Arterial Stiffness Assessed by Cardio-Ankle Vascular Index
Namba, T., Masaki, N., Takase, B., & Adachi, T. K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153664 · Cited by 103
“Therefore, deficiency of NO production caused by endothelial dysfunction increase peripheral arterial resistance, which promotes pulse wave reflection in the central arteries and causes additional stress on the vessel wall leading to intima–media thickening [14].”
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S-Endoglin Expression Is Induced in Senescent Endothelial Cells and Contributes to Vascular Pathology
Blanco, F. J., Grande, M. T., Langa, C., Oujo, B., Velasco, S., Rodríguez‐Barbero, A., Pérez-Gómez, E., Quintanilla, M., López-Novoa, J. M., & Bernabéu, C. (2008) · Circulation Research · doi:10.1161/circresaha.108.176552 · Cited by 101
“Thus, S-endoglin allows a switch that triggers the cardiovascular pathology: (1) upregulation of PAI-1/extracellular matrix (ECM) synthesis may lead to increased fibrosis; (2) downregulation of Id1 is associated with decreased angiogenesis; and (3) downregulation of eNOS and upregulation of COX-2 are involved in hyper…”
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Homocysteine Accelerates Senescence of Endothelial Cells via DNA Hypomethylation of Human Telomerase Reverse Transcriptase
Zhang, D., Sun, X., Liu, J., Xie, X., Cui, W., & Zhu, Y. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303899 · Cited by 96
“Hyperhomocysteinemia-activated oxidative stress might play a crucial role combined with hTERT reduction in EC senescence.(37) The limitations of our study is that we performed no atherosclerotic lesion experiments in vivo to identify whether homocysteine-induced hTERT repression and shortened telomere length is a caus…”
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Endothelial cell senescence and thrombosis: Ageing clots
Bochenek, M. L., Schütz, E., & Schäfer, K. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.09.019 · Cited by 96
Premature aging induced by radiation exhibits pro‐atherosclerotic effects mediated by epigenetic activation of CD 44 expression
Lowe, D., & Raj, K. (2014) · Aging Cell · doi:10.1111/acel.12253 · Cited by 96
Aging-Associated Sensory Neuropathy Alters Pressure-Induced Vasodilation in Humans
Fromy, B., Sigaudo‐Roussel, D., Gaubert‐Dahan, M., Rousseau, P., Abraham, P., Benzoni, D., Berrut, G., & Saumet, J. L. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.279 · Cited by 92
Effect of Aging, MnSOD Deficiency, and Genetic Background on Endothelial Function
Brown, K. A., Didion, S. P., Andresen, J. J., & Faraci, F. M. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.146852 · Cited by 90
“Thus, the goals of this study were (1) to examine the hypothesis that aged mice exhibit increased vascular dysfunction and superoxide levels compared with young animals, (2) to determine whether such changes are greater in MnSOD / mice than in MnSOD / mice, and (3) to determine whether vascular changes with aging and…”
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Authors: BRANDES, R., FLEMING, I., & BUSSE, R.
Affiliations: Goethe University Frankfurt (DE)
Corresponding author: BRANDES, R
ORCID: BRANDES, R
FLEMING, I
Venue: Cardiovascular Research
Publisher: Oxford University Press (OUP)
Published: 2005-05-01
Volume: 66
Issue: 2
Pages: 286-294
ISSN: 0008-6363 (ISSN-L)
DOI: 10.1016/j.cardiores.2004.12.027
OpenAlex: W4256530495
Cited by: 563
References: 0
Citations by year: 2026: 13 · 2025: 19 · 2024: 23 · 2023: 23 · 2022: 38 · 2021: 31 · 2020: 27 · 2019: 26 · 2018: 20 · 2017: 26 · 2016: 32 · 2015: 33 · 2014: 35 · 2013: 25 · 2012: 41
FWCI: 12.98
Type: journal article
Language: en
Open access: closed
Locations: Cardiovascular Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords: endothelial aging, endothelial function, atherosclerosis, coronary artery disease, nitric oxide synthase, inducible nitric oxide synthase, reactive oxygen species, endothelial cell senescence, endothelial cell apoptosis, vascular remodeling, vascular stiffness
MeSH terms: Aged, Aging, Coronary Disease, Endothelium, Vascular, Humans, Vasodilation, Cellular Senescence, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III

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