Characteristics of Vascular Phenotype in Fabry Patients

Area of Science:

• Cardiovascular Medicine
• Genetics
• Lysosomal Storage Disorders

Background:

• Fabry disease is a rare X-linked lysosomal disorder caused by alpha-galactosidase A deficiency.
• This deficiency leads to glycosphingolipid accumulation, primarily in endothelial cells, impairing vascular morphology and function.

Purpose of the Study:

• To assess vascular wall hypertrophy, endothelial function, atherosclerotic plaque presence, and inflammatory biomarkers in Fabry patients compared to healthy controls.
• To characterize the vascular phenotype associated with Fabry disease.

Main Methods:

• Carotid artery intima-media thickness (cIMT) and brachial artery flow-mediated dilation (FMD) were measured.
• Atherosclerotic plaques in carotid and femoral arteries were assessed.
• Levels of endothelial adhesion molecules and inflammatory biomarkers were analyzed in 33 Fabry patients and 66 controls.

Main Results:

• Fabry patients exhibited significantly thicker cIMT, dilated common carotid arteries, and aortic annulus compared to controls.
• Reduced FMD and lower prevalence of atherosclerotic plaques were observed in Fabry patients.
• Elevated levels of vascular cell adhesion molecule-1, interleukin-6, tumor necrosis factor α, and high-sensitivity CRP, along with lower E-selectin, were found in Fabry patients.

Conclusions:

• Fabry disease is associated with a complex vascular phenotype, including structural and functional abnormalities.
• The findings suggest significant endothelial dysfunction and inflammation in Fabry patients.
• Further research into this vascular phenotype may yield important clinical applications for managing Fabry disease.