Arterial Tortuosity Syndrome: An Ascorbate Compartmentalization Disorder?

Area of Science:

• Cardiovascular Research
• Genetics and Molecular Biology
• Connective Tissue Disorders

Background:

• Cardiovascular disorders are a leading cause of death.
• Monogenic heart and vessel disorders offer insights into cardiovascular homeostasis.
• Arterial tortuosity syndrome (ATS) is a rare genetic disorder affecting large arteries, characterized by lengthening, tortuosity, stenosis, and aneurysm formation, linked to connective tissue abnormalities.

Purpose of the Study:

• To elucidate the molecular mechanisms connecting impaired GLUT10 function to arterial malformations in ATS.
• To review current knowledge on ATS and the role of GLUT10 in ascorbate compartmentalization.
• To highlight the potential relevance of ATS research for other vascular dysplasias.

Main Methods:

• Review of existing literature on ATS and GLUT10.
• Analysis of GLUT10's role as a dehydroascorbic acid transporter.
• Examination of GLUT10's involvement in collagen/elastin cross-linking, mitochondrial redox homeostasis, and epigenetic regulation.

Main Results:

• Pathogenic variants in SLC2A10, encoding GLUT10, cause ATS.
• GLUT10 facilitates dehydroascorbic acid transport, crucial for extracellular matrix integrity and cellular redox balance.
• Disrupted GLUT10 function affects collagen and elastin cross-linking, mitochondrial function, and epigenetic regulation.

Conclusions:

• GLUT10 plays a critical role in maintaining vascular health through its involvement in ascorbate transport and related cellular processes.
• Further research into GLUT10's mechanisms is essential for understanding ATS and related vascular diseases.
• Establishing disease models and centralizing patient data are crucial for advancing ATS management and research.