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Stopping Sprouts

Molecular communication between vessel endothelial cells and their support cells underlies vascular malformations

01 July 2023

Stopping Sprouts

Like roads in a city, veins in your body need careful mapping. When they don’t stick to the plan, sporadic vascular malformation – malformed veins – occur, causing pain and disfigurement. These veins form lesions containing genetically faulty cells (mutants). Currently, lesions often recur after treatment. Researchers now search for new therapeutics by growing mutant endothelial cells (ECs), collected from the veins of patients, in dishes. RNA sequencing revealed mutant ECs produced the signalling molecule TGFa. Fluorescence microscopy revealed when supporting cells from lesions (stromal cells) were grown alongside normal ECs, they triggered more EC sprouting (pictured, middle, right) compared with non-lesion stromal cells (left). Next, by grafting mutant ECs into mice, they found EC-produced TGFa triggered stromal cells to release the signalling molecule VEGFA. This caused EC sprouting and malformed veins. Treating mice with afatinib, a drug that interferes with VEGF signalling, decreased lesions, suggesting it may be a useful therapeutic.

Written by Lux Fatimathas

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