Amyloid beta toxicity dependent upon endothelial cell state

Mercedes Balcells, Joseph S. Wallins, Elazer R. Edelman

Research output: Indexed journal article Articlepeer-review

22 Citations (Scopus)

Abstract

Amyloid beta (Aβ), a peptide family produced and deposited in neurons and endothelial cells (EC), is found at subnanomolar concentrations in the plasma of healthy individuals. Simple conformational changes produce a form of Aβ, Aβ42, which creates toxic plaque in the brains of Alzheimer's patients. Oxidative stress induced blood brain barrier degeneration has been proposed as a key factor for Aβ42 toxicity, but cannot account for lack of injury from the same peptide in healthy tissues. We hypothesized that cell state mediates Aβ effect. Thus, we examined the viability of aortic EC, vascular smooth muscle cells (SMC) and epithelial cells (EPI) in different states in the presence of Aβ secreted from transfected Chinese hamster ovary cells (CHO). Aβ was more toxic to all cell types when they were subconfluent. Subconfluent EC sprouted and SMC and EPI were inhibited by Aβ. Confluent EC were virtually resistant to Aβ and suppressed Aβ production by Aβ+CHO. Products of subconfluent EC overcame this resistant state, stimulating the production and toxicity of Aβ42. Confluent EC overgrew ∼35% beyond their quiescent state in the presence of Aβ conditioned in media from subconfluent EC. These findings imply that Aβ42 may well be even more cytotoxic to cells in injured or growth states and potentially explain the variable and potent effects of this protein. One may now need to consider tissue and cell state in addition to local concentration of and exposure duration to Aβ. The specific interactions of Aβ and EC in a state-dependent fashion may help understand further the common and divergent forms of vascular and cerebral toxicity of Aβ and the spectrum of AD.

Original languageEnglish
Pages (from-to)319-322
Number of pages4
JournalNeuroscience Letters
Volume441
Issue number3
DOIs
Publication statusPublished - 29 Aug 2008

Keywords

  • Alzheimer's
  • Amyloid beta
  • Cerebral amyloid angiopathy
  • Endothelium repair

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