Adipose and leptomeningeal arteriole endothelial dysfunction induced by ß-amyloid peptide: a practical human model to study Alzheimer's disease vasculopathy.
J Neurosci Methods
; 235: 123-9, 2014 Sep 30.
Article
in En
| MEDLINE
| ID: mdl-25004204
ABSTRACT
BACKGROUND:
Evidence point to vascular dysfunction and hypoperfusion as early abnormalities in Alzheimer's disease (AD); probing their mechanistic bases can lead to new therapeutic approaches. We tested the hypotheses that ß-amyloid peptide induces endothelial dysfunction and oxidative stress in human microvasculature and that response will be similar between peripheral adipose and brain leptomeningeal arterioles. NEWMETHOD:
Abdominal subcutaneous arterioles from living human subjects (n=17) and cadaver leptomeningeal arterioles (n=6) from rapid autopsy were exposed to Aß1-42 (Aß) for 1-h and dilation response to acetylcholine/papaverine were measured and compared to baseline response. Adipose arteriole reactive oxygen species (ROS) production and nitrotyrosine content were measured. COMPARISON WITH EXISTINGMETHODS:
Methods described allow direct investigation of human microvessel functional response that cannot be replicated by human noninvasive imaging or post-mortem histology.RESULTS:
Adipose arterioles exposed to 2 µM Aß showed impaired dilation to acetylcholine that was reversed by antioxidant polyethylene glycol superoxide dismutase (PEG-SOD) (Aß-60.9 ± 6%, control-93.2 ± 1.8%, Aß+PEGSOD-84.7 ± 3.9%, both p<0.05 vs. Aß). Aß caused reduced dilation to papaverine. Aß increased adipose arteriole ROS production and increased arteriole nitrotyrosine content. Leptomeningeal arterioles showed similar impaired response to acetylcholine when exposed to Aß (43.0 ± 6.2% versus 81.1 ± 5.7% control, p<0.05).CONCLUSION:
Aß exposure induced adipose arteriole endothelial and non-endothelial dysfunction and oxidative stress that were reversed by antioxidant treatment. Aß-induced endothelial dysfunction was similar between peripheral adipose and leptomeningeal arterioles. Ex vivo living adipose and cadaver leptomeningeal arterioles are viable, novel and practical human tissue models to study Alzheimer's vascular pathophysiology.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
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Arterioles
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Adipose Tissue
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Amyloid beta-Peptides
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Endothelial Cells
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Meninges
Limits:
Aged
/
Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Neurosci Methods
Year:
2014
Document type:
Article
Affiliation country:
United States