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Title

Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit

Authors
Fukuda, Andrew
da Silva, Rafaela
Published in Journal of Neuroinflammation. 2012, vol. 9, p. 132
Abstract Aging and atherosclerosis are well-recognized risk factors for cardiac and neurovascular diseases. The Apolipoprotein E deficient (ApoE-/-) mouse on a high-fat diet is a classical model of atherosclerosis, characterized by the presence of atherosclerotic plaques in extracranial vessels but not in cerebral arteries. Increase in arginase activity was shown to participate in vascular dysfunction in the peripheral arteries of atherosclerotic mice by changing the level of nitric oxide (NO). NO plays a key role in the physiological functions of the neurovascular unit (NVU). However, the regulation of arginase expression and activity in the brain was never investigated in association with changes in the NVU, ApoE deficiency and high fat diet.Fourteen-month-old ApoE-/- mice on high-fat diet exhibited deposition of lipids in the NVU, impairment of blood-brain barrier properties, astrogliosis and an increase of aquaporin 4 staining. In association with these changes, brain arginase activity was significantly increased in the old ApoE-/- mice as compared to old wild type mice, with an increase in the level of arginase type I in the blood vessels.In conclusion, aging in this classical mouse model of atherosclerosis induces an increase in the level and activity of arginase I that may impair NO synthesis and contribute to changes in the NVU leading to blood-brain barrier leakage and inflammation.
Keywords Aging/genetics/metabolism/pathologyAnimalsApolipoproteins E/deficiency/geneticsArginase/genetics/metabolismAtherosclerosis/enzymology/genetics/physiopathologyBlood-Brain Barrier/enzymology/physiopathologyDiet, High-Fat/adverse effectsEnzyme Activation/geneticsMiceMice, Inbred C57BLMice, KnockoutNitric Oxide/metabolismUp-Regulation/genetics
Identifiers
PMID: 22709928
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Article (Published version) (2.3 MB) - public document Free access
Structures
Research groups Groupe Gasche Yvan (Soins intensifs) (501)
Groupe Schaller Karl Lothard (neurochirurgie) (851)
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BADAUT, Jérôme et al. Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit. In: Journal of Neuroinflammation, 2012, vol. 9, p. 132. https://archive-ouverte.unige.ch/unige:43600

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Deposited on : 2014-12-17

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