Adipose and leptomeningeal arteriole endothelial dysfunction induced by β-amyloid peptide: A practical human model to study Alzheimer's disease vasculopathy

Seth Truran, Daniel A. Franco, Alex E. Roher, Thomas G. Beach, Camelia Burciu, Geidy Serrano, Chera L. Maarouf, Sara Schwab, Jenna Anderson, Joseph Georges, Peter Reaven, Raymond Q. Migrino

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 β-amyloid peptide induces endothelial dysfunction and oxidative stress in human microvasculature and that response will be similar between peripheral adipose and brain leptomeningeal arterioles. New method: Abdominal subcutaneous arterioles from living human subjects ( n= 17) and cadaver leptomeningeal arterioles ( n= 6) from rapid autopsy were exposed to Aβ1-42 (Aβ) 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 existing methods: 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 Aβ showed impaired dilation to acetylcholine that was reversed by antioxidant polyethylene glycol superoxide dismutase (PEG-SOD) (Aβ-60.9. ±. 6%, control-93.2. ±. 1.8%, Aβ+PEGSOD-84.7. ±. 3.9%, both p<. 0.05 vs. Aβ). Aβ caused reduced dilation to papaverine. Aβ increased adipose arteriole ROS production and increased arteriole nitrotyrosine content. Leptomeningeal arterioles showed similar impaired response to acetylcholine when exposed to Aβ (43.0. ±. 6.2% versus 81.1. ±. 5.7% control, p<. 0.05). Conclusion: Aβ exposure induced adipose arteriole endothelial and non-endothelial dysfunction and oxidative stress that were reversed by antioxidant treatment. Aβ-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.

Original languageEnglish (US)
Pages (from-to)123-129
Number of pages7
JournalJournal of Neuroscience Methods
Volume235
DOIs
StatePublished - Sep 30 2014
Externally publishedYes

Fingerprint

Arterioles
Amyloid
Alzheimer Disease
Acetylcholine
Dilatation
Papaverine
Microvessels
Cadaver
Blood Vessels
Reactive Oxygen Species
Oxidative Stress
peptide A
Antioxidants
Autopsy
Histology
Peptides

Keywords

  • Alzheimer's disease
  • Amyloid
  • Endothelial function
  • Microvessels

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Adipose and leptomeningeal arteriole endothelial dysfunction induced by β-amyloid peptide : A practical human model to study Alzheimer's disease vasculopathy. / Truran, Seth; Franco, Daniel A.; Roher, Alex E.; Beach, Thomas G.; Burciu, Camelia; Serrano, Geidy; Maarouf, Chera L.; Schwab, Sara; Anderson, Jenna; Georges, Joseph; Reaven, Peter; Migrino, Raymond Q.

In: Journal of Neuroscience Methods, Vol. 235, 30.09.2014, p. 123-129.

Research output: Contribution to journalArticle

Truran, S, Franco, DA, Roher, AE, Beach, TG, Burciu, C, Serrano, G, Maarouf, CL, Schwab, S, Anderson, J, Georges, J, Reaven, P & Migrino, RQ 2014, 'Adipose and leptomeningeal arteriole endothelial dysfunction induced by β-amyloid peptide: A practical human model to study Alzheimer's disease vasculopathy', Journal of Neuroscience Methods, vol. 235, pp. 123-129. https://doi.org/10.1016/j.jneumeth.2014.06.014
Truran, Seth ; Franco, Daniel A. ; Roher, Alex E. ; Beach, Thomas G. ; Burciu, Camelia ; Serrano, Geidy ; Maarouf, Chera L. ; Schwab, Sara ; Anderson, Jenna ; Georges, Joseph ; Reaven, Peter ; Migrino, Raymond Q. / Adipose and leptomeningeal arteriole endothelial dysfunction induced by β-amyloid peptide : A practical human model to study Alzheimer's disease vasculopathy. In: Journal of Neuroscience Methods. 2014 ; Vol. 235. pp. 123-129.
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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 β-amyloid peptide induces endothelial dysfunction and oxidative stress in human microvasculature and that response will be similar between peripheral adipose and brain leptomeningeal arterioles. New method: Abdominal subcutaneous arterioles from living human subjects ( n= 17) and cadaver leptomeningeal arterioles ( n= 6) from rapid autopsy were exposed to Aβ1-42 (Aβ) 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 existing methods: 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 Aβ showed impaired dilation to acetylcholine that was reversed by antioxidant polyethylene glycol superoxide dismutase (PEG-SOD) (Aβ-60.9. ±. 6{\%}, control-93.2. ±. 1.8{\%}, Aβ+PEGSOD-84.7. ±. 3.9{\%}, both p<. 0.05 vs. Aβ). Aβ caused reduced dilation to papaverine. Aβ increased adipose arteriole ROS production and increased arteriole nitrotyrosine content. Leptomeningeal arterioles showed similar impaired response to acetylcholine when exposed to Aβ (43.0. ±. 6.2{\%} versus 81.1. ±. 5.7{\%} control, p<. 0.05). Conclusion: Aβ exposure induced adipose arteriole endothelial and non-endothelial dysfunction and oxidative stress that were reversed by antioxidant treatment. Aβ-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.",
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AU - Franco, Daniel A.

AU - Roher, Alex E.

AU - Beach, Thomas G.

AU - Burciu, Camelia

AU - Serrano, Geidy

AU - Maarouf, Chera L.

AU - Schwab, Sara

AU - Anderson, Jenna

AU - Georges, Joseph

AU - Reaven, Peter

AU - Migrino, Raymond Q.

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N2 - 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 β-amyloid peptide induces endothelial dysfunction and oxidative stress in human microvasculature and that response will be similar between peripheral adipose and brain leptomeningeal arterioles. New method: Abdominal subcutaneous arterioles from living human subjects ( n= 17) and cadaver leptomeningeal arterioles ( n= 6) from rapid autopsy were exposed to Aβ1-42 (Aβ) 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 existing methods: 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 Aβ showed impaired dilation to acetylcholine that was reversed by antioxidant polyethylene glycol superoxide dismutase (PEG-SOD) (Aβ-60.9. ±. 6%, control-93.2. ±. 1.8%, Aβ+PEGSOD-84.7. ±. 3.9%, both p<. 0.05 vs. Aβ). Aβ caused reduced dilation to papaverine. Aβ increased adipose arteriole ROS production and increased arteriole nitrotyrosine content. Leptomeningeal arterioles showed similar impaired response to acetylcholine when exposed to Aβ (43.0. ±. 6.2% versus 81.1. ±. 5.7% control, p<. 0.05). Conclusion: Aβ exposure induced adipose arteriole endothelial and non-endothelial dysfunction and oxidative stress that were reversed by antioxidant treatment. Aβ-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.

AB - 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 β-amyloid peptide induces endothelial dysfunction and oxidative stress in human microvasculature and that response will be similar between peripheral adipose and brain leptomeningeal arterioles. New method: Abdominal subcutaneous arterioles from living human subjects ( n= 17) and cadaver leptomeningeal arterioles ( n= 6) from rapid autopsy were exposed to Aβ1-42 (Aβ) 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 existing methods: 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 Aβ showed impaired dilation to acetylcholine that was reversed by antioxidant polyethylene glycol superoxide dismutase (PEG-SOD) (Aβ-60.9. ±. 6%, control-93.2. ±. 1.8%, Aβ+PEGSOD-84.7. ±. 3.9%, both p<. 0.05 vs. Aβ). Aβ caused reduced dilation to papaverine. Aβ increased adipose arteriole ROS production and increased arteriole nitrotyrosine content. Leptomeningeal arterioles showed similar impaired response to acetylcholine when exposed to Aβ (43.0. ±. 6.2% versus 81.1. ±. 5.7% control, p<. 0.05). Conclusion: Aβ exposure induced adipose arteriole endothelial and non-endothelial dysfunction and oxidative stress that were reversed by antioxidant treatment. Aβ-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.

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