Bosentan preserves endothelial function in mice overexpressing APP

Area of Science:

• Neuroscience
• Cardiovascular Biology
• Pharmacology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
• Endothelial dysfunction, a condition affecting blood vessel lining, is increasingly implicated in AD pathogenesis.
• The endothelin system plays a role in vascular tone and may be involved in AD-related vascular changes.

Purpose of the Study:

• To investigate the association between Alzheimer's disease (AD) and endothelial dysfunction.
• To determine if chronic endothelin-1 antagonism can preserve endothelial function in a mouse model of AD.
• To explore the role of the endothelin system in the pathophysiology of AD.

Main Methods:

• Utilized a mouse model overexpressing the amyloid precursor protein (APP) (Tg2576).
• Administered Bosentan, an endothelin receptor antagonist, to Tg2576 mice for 4 months.
• Assessed endothelium-dependent vasorelaxation in aortic and carotid arteries ex vivo.

Main Results:

• Tg2576 mice exhibited significantly attenuated endothelium-dependent aortic and carotid vasorelaxation compared to wild-type controls.
• Treatment with Bosentan restored normal endothelium-dependent vasorelaxation in Tg2576 mice.
• No differences in response to nitroprusside (an endothelium-independent vasodilator) were observed across groups.

Conclusions:

• The study demonstrates endothelial dysfunction in both aortic and carotid arteries of APP-overexpressing mice.
• These findings suggest a pathophysiological role for the endogenous endothelin system in Alzheimer's disease.
• Targeting the endothelin system may offer a therapeutic strategy for AD-related vascular complications.