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The Journal of Neuroscience, April 15, 2002, 22(8):3081-3089

Vitamin E But Not 17-Estradiol Protects against Vascular Toxicity Induced by -Amyloid Wild Type and the Dutch Amyloid Variant

Francisco J. Muñoz¹, Carlos Opazo⁴, Gabriel Gil-Gómez², Gladys Tapia³, Virginia Fernández³, Miguel A. Valverde¹, and Nibaldo C. Inestrosa⁴

¹ Unitat de Senyalització Cel·lular, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona E-08003, Spain, ² Institut Municipal d'Investigació Mèdica (Universitat Pompeu Fabra), Barcelona E-08003, Spain, ³ Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile, and ⁴ Centro de Regulación Celular y Patología, Fondo de Investigación Avanzada en Áreas Prioritarias-Biomedicina and Millenium Institute for Fundamental and Applied Biology, Pontificia Universidad Católica de Chile, Santiago, Chile

Amyloid -peptide (A) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in A yielding A_Glu22Gln. The present study addresses the effect of amyloid fibrils from both wild-type and mutated A on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by A_{1-40 Glu22Gln} and A_{1-40 wild-type} fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that A_Glu22Gln fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of A fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. A_{1-40 wild-type}-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of A fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17-estradiol on vascular damage induced by A_wild-type and A_Glu22Gln. Our data indicate that vitamin E attenuated significantly the A-mediated cytotoxicity on vascular cells, although 17-estradiol and vitamin C failed to inhibit the cytotoxicity induced by A fibrils.

Key words: Alzheimer's disease; CAA; HCHWA-D; amyloid; vitamin E; 17-estradiol; vitamin C; oxidative stress; acetylcholinesterase; endothelial cells; vascular smooth muscle cells

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2283081-09$05.00/0

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