Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells

Mireia Coma, Francesc X. Guix, Gerard Ill-Raga, Iris Uribesalgo, Francesc Alameda, Miguel A. Valverde, Francisco J. Muñoz

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

Cerebral amyloid angiopathy, associated to most cases of Alzheimer's disease (AD), is characterized by the deposition of amyloid ß-peptide (Aß) in brain vessels, although the origin of the vascular amyloid deposits is still controversial: neuronal versus vascular. In the present work, we demonstrate that primary cultures of human cerebral vascular smooth muscle cells (HC-VSMCs) have all the secretases involved in amyloid ß-protein precursor (APP) cleavage and produce Aß1-40 and Aß1-42. Oxidative stress, a key factor in the etiology and pathophysiology of AD, up-regulates ß-site APP cleaving enzyme 1 (BACE1) expression, as well as Aß1-40 and Aß1-42 secretion in HC-VSMCs. This process is mediated by c-Jun N-terminal Kinase and p38 MAPK signaling and appears restricted to BACE1 regulation as no changes in the other secretases were observed. In conclusion, oxidative stress-mediated up-regulation of the amyloidogenic pathway in human cerebral vascular smooth muscle cells may contribute to the overall cerebrovascular amyloid angiopathy observed in AD patients. © 2007 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)969-980
JournalNeurobiology of Aging
Volume29
Issue number7
DOIs
Publication statusPublished - 1 Jul 2008

Keywords

  • Alzheimer's disease
  • Amyloid ß-peptide
  • BACE1
  • C-JNK
  • Oxidative stress
  • p38 MAPK
  • Vascular smooth muscle cells

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