Skip to search boxSkip to navigationSkip to main content

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

  • Leocadio Rodríguez-Mañas
    ,
  • Mariam El-Assar
    ,
  • Susana Vallejo
    ,
  • Pedro López-Dóriga
    ,
  • Joaquin Solís
    ,
  • Roberto Petidier
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 226-238

Journal (Volume, Issue Number)

Aging Cell (Volume 8, Issue 3)

Publication milestones

  • Published - 01/06/2009

Publication status

Published - 01/06/2009

ISSN

1474-9718

External Publication IDs

  • handle.net: 10547/593446
  • Scopus: 66249112184

Access to documents

Publication metrics

PlumX, opens in new tab

Mentions
1
Captures
117
191