Enhanced L-arginine-induced vasoreactivity suggests endothelial dysfunction in CADASIL

Area of Science:

• Neurology
• Vascular Biology
• Genetics

Background:

• Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is caused by Notch3 gene mutations, leading to stroke and dementia.
• Pathological hallmarks include arterial granular deposits and smooth muscle cell degeneration.
• Endothelial function in CADASIL remains poorly understood, despite its importance in cerebrovascular health.

Purpose of the Study:

• To assess endothelial function in CADASIL patients by measuring L-arginine-induced vasoreactivity.
• To compare cerebral hemodynamic parameters between CADASIL patients and healthy controls.

Main Methods:

• Transcranial Doppler sonography was used to measure middle cerebral artery blood flow velocity and pulsatility index.
• L-arginine, a substrate for nitric oxide synthase, was administered to assess endothelial-dependent vasoreactivity.
• 25 CADASIL patients and 24 non-CADASIL controls were included.

Main Results:

• CADASIL patients showed reduced resting mean flow velocity and increased pulsatility index compared to controls.
• L-arginine administration significantly increased vasoreactivity in CADASIL patients compared to controls.
• A significant reduction in pulsatility index was observed after L-arginine in CADASIL patients, indicating improved vasodilation.

Conclusions:

• Impaired cerebral hemodynamics and endothelial dysfunction likely play a pathogenic role in CADASIL.
• The enhanced L-arginine vasoreactivity in CADASIL suggests potential therapeutic targets.
• Findings may offer insights into treating sporadic small vessel diseases as well.