Bosentan preserves endothelial function in mice overexpressing APP


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2006
Contact PI Name:
Amir Lerman
Contact PI Affiliation:
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
Co-Authors:
A.A. Elesber, P.O. Bonetti, J.E. Woodrum, X.Y. Zhu, L.O. Lerman, S.G. Younkin
Primary Reference (PubMED ID):
Funding Source:
Miami Heart Research Institute
National Heart Lung and Blood Institute (NHLBI)
Study Goal and Principal Findings:

This study investigated endothelial dysfunction in Alzheimer's disease by testing bosentan, an antagonist of the vasoconstricting peptide endothelin-1 (ET-1), on Tg2576 mice. Past studies have demonstrated Aβ may induce endothelial dysfunction of cerebral and systemic vessels, and several findings suggest that vascular factors may play a major role in Alzheimer's disease. Results in this study show endothelium-dependent aortic vasorelaxation being attenuated in Tg2576 mice, compared to both wildtype and Tg2576 mice treated with bosentan. There was no difference between the three groups in response to nitroprusside. This study demonstrates endothelial dysfunction in the arteries of mice overexpressing APP and suggests a pathophysiological role for the endothelial system in AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Bosentan
Therapeutic Target:
Endothelin Receptor Type A
Therapeutic Target:
Endothelin Receptor Type B

Animal Model

Model Information:
Species:
Mouse
Model Type:
Non-transgenic
Strain/Genetic Background:
C57BL/6
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Biochemical
Endothelin Converting Enzyme 1 (ECE1)
Electrophysiology
Vascular Reactivity
Vasorelaxation
Physiology
Blood Pressure

Source URL: http://alzped.nia.nih.gov/bosentan-preserves-endothelial