The DOI matches its Crossref record; 95 of the 96 references it cites were found in a registry or an index.
The AGE-RAGE Axis: Implications for Age-Associated Arterial Diseases
Open accessAbstract
The process of advanced glycation leads to the generation and accumulation of an heterogeneous class of molecules called advanced glycation endproducts, or AGEs. AGEs are produced to accelerated degrees in disorders such as diabetes, renal failure, inflammation, neurodegeneration and in aging. Further, AGEs are present in foods and in tobacco products. Hence, through both endogenous production and exogenous consumption, AGEs perturb vascular homeostasis by a number of means; in the first case, AGEs can cause cross-linking of long-lived molecules in the basement membranes such as collagens, thereby leading to “vascular stiffening” and processes that lead to hyperpermeability and loss of structural integrity. Second, AGEs interaction with their major cell surface signal transduction receptor for AGE or RAGE sets off a cascade of events leading to modulation of gene expression and loss of vascular and tissue homeostasis, processes that contribute to cardiovascular disease. In addition, it has been shown that an enzyme, which plays key roles in the detoxification of pre-AGE species, glyoxalase 1 (GLO1), is reduced in aged and diabetic tissues. In the diabetic kidney devoid of Ager (gene encoding RAGE), higher levels of Glo1 mRNA and GLO1 protein and activity were observed, suggesting that in conditions of high AGE accumulation, natural defenses may be mitigated, at least in part through RAGE. AGEs are a marker of arterial aging and may be detected by both biochemical means, as well as measurement of “skin autofluorescence.” In this review, we will detail the pathobiology of the AGE-RAGE axis and the consequences of its activation in the vasculature and conclude with potential avenues for therapeutic interruption of the AGE-RAGE ligand-RAGE pathways as means to forestall the deleterious consequences of AGE accumulation and signaling via RAGE.
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“RAGE, a member of the immunoglobulin superfamily of pattern recognition receptors, is not known to be related to oxytocin or oxytocin signalling22–33.”
From Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice (2019) · cites this paper as [22]
In the citing paper
“The interaction of AGE-RAGE triggers intracellular and extracellular signaling pathways through the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), NADPH oxidase, and nuclear factor-κB (NF-κB).”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [39]
In the citing paper
“Activation of these proteins usually increases oxidative stress and inflammation that, in turn, promotes RAGE expression in a positive feed-forward loop, contributing to chronic disease development39–41.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [39]
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Executive Summary: Heart Disease and Stroke Statistics—2016 Update
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Advanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury
Goldin, A., Beckman, J. A., Schmidt, A. M., & Creager, M. A. (2006) · Circulation · doi:10.1161/circulationaha.106.621854 · Cited by 2,261
Self-citationLakatta, E. G., & Levy, D. (2003) · Circulation · doi:10.1161/01.cir.0000048892.83521.58 · Cited by 2,244
Arterial Stiffness and Risk of Coronary Heart Disease and Stroke: The Rotterdam Study
Mattace-Raso, F. U. S., van der Cammen, T. J. M., Hofman, A., van Popele, N. M., Bos, M. L., Schalekamp, M. A. D. H., Asmar, R., Reneman, R. S., Hoeks, A. P. G., Breteler, M. M. B., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.555235 · Cited by 1,914 · cited 1×
“Arterial stiffness is associated with greater risk for aging-associated cardio- and cerebrovascular diseases and mortality (Laurent et al., 2001; Mattace-Raso et al., 2006; Kaess et al., 2012).”
BackgroundAdvanced Glycation End Products and Diabetic Complications
Singh, V. P., Bali, A., Singh, N., & Jaggi, A. S. (2014) · The Korean Journal of Physiology & Pharmacology · doi:10.4196/kjpp.2014.18.1.1 · Cited by 1,518
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Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411
Understanding the role of the perivascular space in cerebral small vessel disease
Brown, R., Benveniste, H., Black, S. E., Charpak, S., Dichgans, M., Joutel, A., Nedergaard, M., Smith, K. J., Zloković, B. V., & Wardlaw, J. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy113 · Cited by 346
Interaction Between Hypertension and Arterial Stiffness
Safar, M. E., Asmar, R. G., Bénétos, A., Blacher, J., Boutouyrie, P., Lacolley, P. J., Laurent, S., London, G. M., Pannier, B., Protogerou, A. D., et al. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11212 · Cited by 307
Shen, C., Lu, C., Wu, C.-H., Li, K., Kuo, Y., Hsieh, S., & Yu, C. (2020) · Molecules · doi:10.3390/molecules25235591 · Cited by 316
Chen, Y., Zhao, X., & Wu, H. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.313131 · Cited by 254
Metadata
- Authors
- Senatus, L. M., & Schmidt, A. M.
- Affiliations
- New York University (US)
- Corresponding author
- Schmidt, Ann Marie
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2017-12-05
- Volume
- 8
- Pages
- 187-187
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC5723304
- OpenAlex
- W2774984051
- Cited by
- 167
- References
- 96
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 17 · 2023: 18 · 2022: 29 · 2021: 23 · 2020: 19 · 2019: 17 · 2018: 10
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Public Health Service
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- advanced glycation end products, AGE-RAGE axis, receptor for advanced glycation end products, vascular aging, arterial aging, arterial stiffness, glyoxalase I, diabetes mellitus, diabetic kidney, skin autofluorescence, AGE accumulation, cardiovascular disease, vascular homeostasis
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