Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation

2.50
Hdl Handle:
http://hdl.handle.net/10547/593446
Title:
Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation
Authors:
Rodríguez-Mañas, Leocadio; El-Assar, Mariam; Vallejo, Susana; López-Dóriga, Pedro; Solís, Joaquin; Petidier, Roberto; Montes, Manuel; Nevado, Julián; Castro, Marta; Gómez-Guerrero, Carmen; Peiró, Concepción; Sánchez-Ferrer, Carlos F
Abstract:
Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18-91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin-induced relaxation was due to nitric oxide release while the rest was sensitive to cyclooxygenase (COX) blockade. In microvessels from subjects older than 60 years, this COX-derived vasodilatation was lost but a COX-derived vasoconstriction occurred. Evidence for age-related vascular oxidant and inflammatory environment was observed, which could be related to the development of endothelial dysfunction. Indeed, aged microvessels showed superoxide anions (O(2)(-)) and peroxynitrite (ONOO(-)) formation, enhancement of NADPH oxidase and inducible NO synthase expression. Pharmacological interference of COX, thromboxane A(2)/prostaglandin H(2) receptor, O(2)(-), ONOO(-), inducible NO synthase, and NADPH oxidase improved the age-related endothelial dysfunction. In situ vascular nuclear factor-kappaB activation was enhanced with age, which correlated with endothelial dysfunction. We conclude that the age-dependent endothelial dysfunction in human vessels is due to the combined effect of oxidative stress and vascular wall inflammation.
Citation:
Rodríguez-Mañas, L. et al (2009) 'Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation' Aging Cell 8 (3):226-38
Publisher:
Wiley
Journal:
Aging cell
Issue Date:
Jun-2009
URI:
http://hdl.handle.net/10547/593446
DOI:
10.1111/j.1474-9726.2009.00466.x
PubMed ID:
19245678
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2009.00466.x/full
Type:
Article
Language:
en
ISSN:
1474-9726
Appears in Collections:
IHR Institute for Health Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRodríguez-Mañas, Leocadioen
dc.contributor.authorEl-Assar, Mariamen
dc.contributor.authorVallejo, Susanaen
dc.contributor.authorLópez-Dóriga, Pedroen
dc.contributor.authorSolís, Joaquinen
dc.contributor.authorPetidier, Robertoen
dc.contributor.authorMontes, Manuelen
dc.contributor.authorNevado, Juliánen
dc.contributor.authorCastro, Martaen
dc.contributor.authorGómez-Guerrero, Carmenen
dc.contributor.authorPeiró, Concepciónen
dc.contributor.authorSánchez-Ferrer, Carlos Fen
dc.date.accessioned2016-01-14T11:56:08Zen
dc.date.available2016-01-14T11:56:08Zen
dc.date.issued2009-06en
dc.identifier.citationRodríguez-Mañas, L. et al (2009) 'Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation' Aging Cell 8 (3):226-38en
dc.identifier.issn1474-9726en
dc.identifier.pmid19245678en
dc.identifier.doi10.1111/j.1474-9726.2009.00466.xen
dc.identifier.urihttp://hdl.handle.net/10547/593446en
dc.description.abstractVascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18-91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin-induced relaxation was due to nitric oxide release while the rest was sensitive to cyclooxygenase (COX) blockade. In microvessels from subjects older than 60 years, this COX-derived vasodilatation was lost but a COX-derived vasoconstriction occurred. Evidence for age-related vascular oxidant and inflammatory environment was observed, which could be related to the development of endothelial dysfunction. Indeed, aged microvessels showed superoxide anions (O(2)(-)) and peroxynitrite (ONOO(-)) formation, enhancement of NADPH oxidase and inducible NO synthase expression. Pharmacological interference of COX, thromboxane A(2)/prostaglandin H(2) receptor, O(2)(-), ONOO(-), inducible NO synthase, and NADPH oxidase improved the age-related endothelial dysfunction. In situ vascular nuclear factor-kappaB activation was enhanced with age, which correlated with endothelial dysfunction. We conclude that the age-dependent endothelial dysfunction in human vessels is due to the combined effect of oxidative stress and vascular wall inflammation.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2009.00466.x/fullen
dc.rightsArchived with thanks to Aging cellen
dc.subjectagingen
dc.subjectcyclooxygenaseen
dc.subjectendotheliumen
dc.subjectnitric oxideen
dc.subjectnuclear factor kappa-Ben
dc.subjectperoxynitriteen
dc.subjectsuperoxideen
dc.subjectvascular inflammationen
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAgingen
dc.subject.meshEndothelium, Vascularen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshInflammation Mediatorsen
dc.subject.meshMaleen
dc.subject.meshMesenteric Arteriesen
dc.subject.meshMiddle Ageden
dc.subject.meshNF-kappa Ben
dc.subject.meshNitric Oxideen
dc.subject.meshOxidative Stressen
dc.subject.meshProstaglandin-Endoperoxide Synthasesen
dc.subject.meshSuperoxidesen
dc.subject.meshVasodilationen
dc.titleEndothelial dysfunction in aged humans is related with oxidative stress and vascular inflammationen
dc.typeArticleen
dc.identifier.journalAging cellen

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