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

Article Article scientifique Article Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit eng 2012 author Badaut Jérôme 677098 author Copin Jean-Christophe 524456 author Fukuda Andrew author Gasche Yvan 32923 author Schaller Karl Lothard 658606 author da Silva Rafaela 132 10.1186/1742-2094-9-132 22709928 1742-2094 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. Aging/genetics/metabolism/pathology Animals Apolipoproteins E/deficiency/genetics Arginase/genetics/metabolism Atherosclerosis/enzymology/genetics/physiopathology Blood-Brain Barrier/enzymology/physiopathology Diet, High-Fat/adverse effects Enzyme Activation/genetics Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide/metabolism Up-Regulation/genetics Dewey 616.8 Dewey 617 61 Département des neurosciences cliniques 226 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 255 Groupe Gasche Yvan (Soins intensifs) 501 513 Groupe Schaller Karl Lothard (neurochirurgie) 851 Journal of neuroinflammation 9 8653af2c-ea5d-4754-90d6-43dd7ba34b75 Article (Published version) Public Increase of arginase activity in old apolipoprotein-E deficient mice.pdf 2419976 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit	Journal of neuroinflammation			2012	581	228

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Badaut, Jérôme