Arterial Tortuosity Syndrome: An Ascorbate Compartmentalization Disorder?

Critical Issues: Although several hypotheses have been forwarded, the molecular mechanisms linking disrupted GLUT10 activity with arterial malformations are largely unknown. Recent Advances: The vascular and systemic manifestations and natural history of ATS patients have been largely delineated. GLUT10 was identified as an intracellular transporter of dehydroascorbic acid, which contributes to collagen and elastin cross-linking in the endoplasmic reticulum, redox homeostasis in the mitochondria, and global and gene-specific methylation/hydroxymethylation affecting epigenetic regulation in the nucleus. We revise here the current knowledge on ATS and the role of GLUT10 within the compartmentalization of ascorbate in physiological and diseased states. Future Directions: Centralization of clinical, treatment, and outcome data will enable better management for ATS patients. Establishment of representative animal disease models could facilitate the study of pathomechanisms underlying ATS. This might be relevant for other forms of vascular dysplasia, such as isolated aneurysm formation, hypertensive vasculopathy, and neovascularization. Antioxid. Redox Signal. 00, 000-000.

Automated summary

The molecular mechanisms linking disrupted GLUT10 activity with arterial malformations in ATS patients are largely unknown. Recent advances have outlined the role of GLUT10 as an intracellular transporter and its impact on collagen and elastin cross-linking, redox homeostasis, and epigenetic regulation. Future research directions include centralizing clinical data for better patient management and establishing representative animal disease models to study pathomechanisms underlying ATS.