A microfluidic approach to reassess therapeutic strategies for vascular Ehlers-Danlos syndrome from an endothelial perspective – a proof of concept

Vascular Ehlers-Danlos syndrome (vEDS) is a genetic disorder caused by mutations in the gene coding for collagen type III, leading to fragile tissues and a higher risk of arterial, uterine, and bowel ruptures. These ruptures, particularly arterial, are the leading cause of death in vEDS patients. Currently, there is no specific treatment for vEDS. Arterial ruptures occur when the artery wall weakens due to defective collagen III production. We propose targeting the endothelial cells (ECs) lining the artery walls, which are more accessible than the fibroblasts that produce collagen, as a potential treatment approach. The idea is to strengthen the artery's resistance to blood pressure by enhancing the basement membrane’s support role, independent of collagen III. Using a microfluidic platform, we aim to identify components of the basement membrane that can increase artery strength. The inclusion of patient-derived fibroblasts in the proposed microfluidic system to replicate vEDS pathology and assess arterial wall susceptibility to rupture could be used as a personalized medicine approach. Additionally, future therapies might involve increasing basement membrane protein expression in ECs to compensate for the weakened artery walls in vEDS patients.