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Neurobiol Aging. 2000 Mar-Apr;21(2):183-97.

Soluble beta-amyloid peptides mediate vasoactivity via activation of a pro-inflammatory pathway.

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1
The Roskamp Institute, University of South Florida, 3515 E. Fletcher Ave., 33613, Tampa, FL, USA. dparis@com1.med.usf.edu

Abstract

Freshly solubilized beta-amyloid (Abeta) peptides display vasoactive properties, increasing both the magnitude and the duration of endothelin-1-induced vasoconstriction. We show that Abeta vasoactivity is mediated by the stimulation of a pro-inflammatory pathway involving activation of secretory phospholipase A(2) (PLA(2)), mitogen activated protein kinase (MAPK) kinase (MEK1/2), p38 MAPK, cytosolic PLA(2), and the release of arachidonic acid. Ultimately, arachidonic acid is metabolized into proinflammatory eicosanoids via the 5-lipoxygenase and cyclooxygenase-2 (COX-2) enzymes, both of which we show to be required for A beta vasoactivity. Accordingly, p38 MAPK activity is higher in the brains of transgenic mice that overproduce A beta, and COX-2 immunoreactivity is increased in the cerebrovasculature of these transgenic animals. Taken together, our data show that freshly solubilized A beta peptides can trigger a pro-inflammatory reaction in the vasculature that can be blocked by inhibiting specific target molecules, providing the basis for novel therapeutic intervention.

PMID:
10867203
[Indexed for MEDLINE]

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