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Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc


Shi, Yi; Savarese, Gianluigi; Perrone-Filardi, Pasquale; Lüscher, Thomas F; Camici, Giovanni G (2014). Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc. International Journal of Cardiology, 175(3):446-450.

Abstract

BACKGROUND: Aging is an independent risk factor for cardiovascular and cerebrovascular disease. To date, little is known about the mechanisms of aging of cerebral arteries and whether the aging gene p66(Shc) is implicated in it. The present study was designed to assess age-induced vascular dysfunction in cerebral and systemic arteries of wild type (wt) and p66(Shc-/-) mice.
METHODS: Basilar arteries and size matched second order femoral arteries of 3-month (3M), 6-month (6M) and 2-year old (2Y) mice were studied in wt and p66(Shc-/-) mice. To assess vascular function, arterial rings mounted in a myograph for isometric tension recordings were exposed to increasing concentrations of acetylcholine and sodium nitroprusside. Reactive oxygen species (ROS) generation was assessed in femoral and basilar arteries using the spin trap 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine.
RESULTS: In wt mice, endothelial function of the femoral artery was not affected by age unlike in the basilar artery where an age-dependent dysfunction was observed. In p66(Shc-/-) a similar response was observed in the femoral artery; however, age-dependent endothelial dysfunction of the basilar artery was blunted as compared to wt. Levels of ROS were comparable in the femoral arteries of 3M and 2Y of wt and p66(Shc-/-) mice. Differently, ROS levels in the basilar artery of wt mice were strongly increased by age unlike in p66(Shc-/-) mice where they remained comparable irrespective of age.
CONCLUSIONS: Endothelial function in cerebral arteries, but not in size-matched systemic ones, is heavily impaired by aging. This process is paralleled by an increased ROS production and is mediated by the p66(Shc) gene.

Abstract

BACKGROUND: Aging is an independent risk factor for cardiovascular and cerebrovascular disease. To date, little is known about the mechanisms of aging of cerebral arteries and whether the aging gene p66(Shc) is implicated in it. The present study was designed to assess age-induced vascular dysfunction in cerebral and systemic arteries of wild type (wt) and p66(Shc-/-) mice.
METHODS: Basilar arteries and size matched second order femoral arteries of 3-month (3M), 6-month (6M) and 2-year old (2Y) mice were studied in wt and p66(Shc-/-) mice. To assess vascular function, arterial rings mounted in a myograph for isometric tension recordings were exposed to increasing concentrations of acetylcholine and sodium nitroprusside. Reactive oxygen species (ROS) generation was assessed in femoral and basilar arteries using the spin trap 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine.
RESULTS: In wt mice, endothelial function of the femoral artery was not affected by age unlike in the basilar artery where an age-dependent dysfunction was observed. In p66(Shc-/-) a similar response was observed in the femoral artery; however, age-dependent endothelial dysfunction of the basilar artery was blunted as compared to wt. Levels of ROS were comparable in the femoral arteries of 3M and 2Y of wt and p66(Shc-/-) mice. Differently, ROS levels in the basilar artery of wt mice were strongly increased by age unlike in p66(Shc-/-) mice where they remained comparable irrespective of age.
CONCLUSIONS: Endothelial function in cerebral arteries, but not in size-matched systemic ones, is heavily impaired by aging. This process is paralleled by an increased ROS production and is mediated by the p66(Shc) gene.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:20 August 2014
Deposited On:12 Feb 2015 11:36
Last Modified:08 Dec 2017 11:02
Publisher:Elsevier
ISSN:0167-5273
Publisher DOI:https://doi.org/10.1016/j.ijcard.2014.06.025
PubMed ID:25012499

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