Amyloid β-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells

Emmanuelle M. Blanc, Michal Toborek, Robert J. Mark, Bernhard Hennig, Mark P. Mattson

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Amyloid β-peptide (Aβ) is deposited as insoluble fibrils in the brain parenchyma and cerebral blood vessels in Alzheimer's disease (AD). In addition to neuronal degeneration, cerebral vascular alterations indicative of damage to vascular endothelial cells and disruption of the blood-brain barrier occur in AD. Here we report that Aβ25-35 can impair regulatory functions of endothelial cells (ECs) from porcine pulmonary artery and induce their death. Subtoxic exposures to Aβ25-35 induced albumin transfer across EC monolayers and impaired glucose transport into ECs. Cell death induced by Aβ25-35 was of an apoptotic form, characterized by DNA condensation and fragmentation, and prevented by inhibitors of macromolecular synthesis and endonucleases. The effects of Aβ25-35 were specific because Aβ1-40 also induced apoptosis in ECs with the apoptotic cells localized to the microenvironment of Aβ1-40 aggregates and because astrocytes did not undergo similar changes after exposure to Aβ25-35. Damage and death of ECs induced by Aβ25-35 were attenuated by antioxidants, a calcium channel blocker, and a chelator of intracellular calcium, indicating the involvement of free radicals and dysregulation of calcium homeostasis. The data show that Aβ induces increased permeability of EC monolayers to macromolecules, impairs glucose transport, and induces apoptosis. It similar mechanisms are operative in vivo, then Aβ and other amyloidogenic peptides may be directly involved in vascular EC damage documented in AD and other disorders that involve vascular amyloid accumulation.

Original languageEnglish (US)
Pages (from-to)1870-1881
Number of pages12
JournalJournal of neurochemistry
Volume68
Issue number5
DOIs
StatePublished - May 1997

Keywords

  • Alzheimer's disease
  • Bloodbrain barrier
  • Calcium homeostasis
  • Endonuclease inhibitor
  • Free radicals
  • Glucose transport
  • Hydrogen peroxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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