Arterial Tortuosity Syndrome: An Ascorbate Compartmentalization Disorder?

Significance: Cardiovascular disorders are the most important cause of morbidity and mortality in Western world. Monogenic developmental heart vessels highly valuable to study physiological pathological processes cardiovascular system homeostasis. The arterial tortuosity syndrome (ATS) is a rare, autosomal recessive connective tissue disorder showing lengthening, tortuosity, stenosis large arteries, with propensity for aneurysm formation. In histopathology, it associates fragmentation disorganization elastic fibers several tissues, including wall. ATS caused by pathogenic variants SLC2A10 encoding facilitative glucose transporter (GLUT)10. Critical Issues: Although hypotheses have been forwarded, molecular mechanisms linking disrupted GLUT10 activity malformations largely unknown. Recent Advances: vascular systemic manifestations natural history patients delineated. was identified as an intracellular dehydroascorbic acid, which contributes collagen elastin cross-linking endoplasmic reticulum, redox homeostasis mitochondria, global gene-specific methylation/hydroxymethylation affecting epigenetic regulation nucleus. We revise here current knowledge on role within compartmentalization ascorbate diseased states. Future Directions: Centralization clinical, treatment, outcome data will enable better management patients. Establishment representative animal disease models could facilitate pathomechanisms underlying ATS. This might be relevant other forms dysplasia, such isolated formation, hypertensive vasculopathy, neovascularization. Antioxid. Redox Signal. 34, 875–889.