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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

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

Authors: Jérôme Badaut, Jean-Christophe Copin, Andrew M Fukuda, Yvan Gasche, Karl Schaller, Rafaela F da Silva

Published in: Journal of Neuroinflammation | Issue 1/2012

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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.
Literature
1.
Meir KS, Leitersdorf E: Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. Arterioscler Thromb Vasc Biol 2004, 24:1006–1014.CrossRefPubMed
2.
Landmesser U, Hornig B, Drexler H: Endothelial function: a critical determinant in atherosclerosis? Circulation 2004, 109:II27-II33.CrossRefPubMed
3.
Libby P: Inflammation in atherosclerosis. Nature. 2002, 420:868–874.PubMed
4.
Stoll G, Bendszus M: Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 2006, 37:1923–1932.CrossRefPubMed
5.
Kawashima S: The two faces of endothelial nitric oxide synthase in the pathophysiology of atherosclerosis. Endothelium 2004, 11:99–107.CrossRefPubMed
6.
Kawashima S, Yokoyama M: Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 2004, 24:998–1005.CrossRefPubMed
7.
8.
Kim JH, Bugaj LJ, Oh YJ, Bivalacqua TJ, Ryoo S, Soucy KG, Santhanam L, Webb A, Camara A, Sikka G, Nyhan D, Shoukas AA, Ilies M, Christianson DW, Champion HC, Berkowitz DE: Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats. J Appl Physiol 2009, 107:1249–1257.CrossRefPubMedPubMedCentral
9.
White AR, Ryoo S, Li D, Champion HC, Steppan J, Wang D, Nyhan D, Shoukas AA, Hare JM, Berkowitz DE: Knockdown of arginase I restores NO signaling in the vasculature of old rats. Hypertension 2006, 47:245–251.CrossRefPubMed
10.
Napoli C, Witztum JL, de Nigris F, Palumbo G, D’Armiento FP, Palinski W: Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries. Circulation 1999, 99:2003–2010.CrossRefPubMed
11.
Crisby M, Rahman SM, Sylven C, Winblad B, Schultzberg M: Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice. Implications for Alzheimer’s disease and stroke. Neurosci Lett 2004, 369:87–92.CrossRefPubMed
12.
Mato M, Ookawara S, Mashiko T, Sakamoto A, Mato TK, Maeda N, Kodama T: Regional difference of lipid distribution in brain of apolipoprotein E deficient mice. Anat Rec 1999, 256:165–176.CrossRefPubMed
13.
Masliah E, Samuel W, Veinbergs I, Mallory M, Mante M, Saitoh T: Neurodegeneration and cognitive impairment in apoE-deficient mice is ameliorated by infusion of recombinant apoE. Brain Res 1997, 751:307–314.CrossRefPubMed
14.
Methia N, Andre P, Hafezi-Moghadam A, Economopoulos M, Thomas KL, Wagner DD: ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med 2001, 7:810–815.PubMedPubMedCentral
15.
Hafezi-Moghadam A, Thomas KL, Wagner DD: ApoE deficiency leads to a progressive age-dependent blood–brain barrier leakage. Am J Physiol Cell Physiol 2007, 292:C1256-C1262.CrossRefPubMed
16.
Iadecola C, Pelligrino DA, Moskowitz MA, Lassen NA: Nitric oxide synthase inhibition and cerebrovascular regulation. J Cereb Blood Flow Metab 1994, 14:175–192.CrossRefPubMed
17.
Liu P, Smith PF, Appleton I, Darlington CL, Bilkey DK: Regional variations and age-related changes in nitric oxide synthase and arginase in the sub-regions of the hippocampus. Neuroscience 2003, 119:679–687.CrossRefPubMed
18.
Liu P, Smith PF, Appleton I, Darlington CL, Bilkey DK: Age-related changes in nitric oxide synthase and arginase in the rat prefrontal cortex. Neurobiol Aging 2004, 25:547–552.CrossRefPubMed
19.
Yu H, Iyer RK, Kern RM, Rodriguez WI, Grody WW, Cederbaum SD: Expression of arginase isozymes in mouse brain. J Neurosci Res 2001, 66:406–422.CrossRefPubMed
20.
Thacher TN, Gambillara V, Riche F, Silacci P, Stergiopulos N, da Silva RF: Regulation of arginase pathway in response to wall shear stress. Atherosclerosis 2010, 210:63–70.CrossRefPubMed
21.
Ming XF, Barandier C, Viswambharan H, Kwak BR, Mach F, Mazzolai L, Hayoz D, Ruffieux J, Rusconi S, Montani JP, Yang Z: Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction. Circulation 2004, 110:3708–3714.CrossRefPubMed
22.
Cheng C, Tempel D, van Haperen R, van der Baan A, Grosveld F, Daemen MJ, Krams R, de Crom R: Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 2006, 113:2744–2753.CrossRefPubMed
23.
Hirt L, Price M, Ternon B, Mastour N, Brunet JF, Badaut J: Early induction of AQP4 contributes the limitation of the edema formation in the brain ischemia. J Cereb Blood Flow Metab 2009, 29:423–433.CrossRefPubMed
24.
Badaut J, Ashwal S, Adami A, Tone B, Recker R, Spagnoli D, Ternon B, Obenaus A: Brain water mobility decreases after astrocytic aquaporin-4 inhibition using RNA interference. J Cereb Blood Flow Metab 2011, 31:819–831.CrossRefPubMed
25.
Wang R, Ashwal S, Tone B, Tian HR, Badaut J, Rasmussen A, Obenaus A: Albumin reduces blood–brain barrier permeability but does not alter infarct size in a rat model of neonatal stroke. Pediatr Res 2007, 62:261–266.CrossRefPubMed
26.
Uranga RM, Keller JN: Diet and age interactions with regards to cholesterol regulation and brain pathogenesis. Curr Gerontol Geriatr Res 2010, 2010:219683.CrossRefPubMedCentral
27.
Kropf P, Fuentes JM, Fahnrich E, Arpa L, Herath S, Weber V, Soler G, Celada A, Modolell M, Muller I: Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo. FASEB J 2005, 19:1000–1002.PubMed
28.
Ozaki M, Kawashima S, Yamashita T, Hirase T, Namiki M, Inoue N, Hirata K, Yasui H, Sakurai H, Yoshida Y, Masada M, Yokoyama M: Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice. J Clin Invest 2002, 110:331–340.CrossRefPubMedPubMedCentral
29.
Ryoo S, Gupta G, Benjo A, Lim HK, Camara A, Sikka G, Lim HK, Sohi J, Santhanam L, Soucy K, Tuday E, Baraban E, Ilies M, Gerstenblith G, Nyhan D, Shoukas A, Christianson DW, Alp NJ, Champion HC, Huso D, Berkowitz DE: Endothelial arginase II: a novel target for the treatment of atherosclerosis. Circ Res 2008, 102:923–932.CrossRefPubMed
30.
Yang B, Zador Z, Verkman AS: Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem 2008, 283:15280–15286.CrossRefPubMedPubMedCentral
31.
Liu P, Smith PF, Appleton I, Darlington CL, Bilkey DK: Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: regional variations and age-related changes. Hippocampus 2003, 13:859–867.CrossRefPubMed
32.
Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM: Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003, 108:2000–2006.CrossRefPubMed
33.
Law A, Gauthier S, Quirion R: Alteration of nitric oxide synthase activity in young and aged apolipoprotein E-deficient mice. Neurobiol Aging 2003, 24:187–190.CrossRefPubMed
Metadata
Title
Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit
Authors
Jérôme Badaut
Jean-Christophe Copin
Andrew M Fukuda
Yvan Gasche
Karl Schaller
Rafaela F da Silva
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-132

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