Arteriovenous malformations (AVMs) are abnormal and direct connections between arteries and veins, causing disorganised blood flow and weak vessel structure. Although nosebleeds are a common clinical outcome of AVMs, more serious hemorrhages in the brain and lungs can occur. Corti et al. studied AVMs in zebrafish embryos carrying a mutant version of activin receptor-like kinase 1 (alk1), which is associated with hemorrhagic telangiectasia type 2 (HTT2), a vascular disorder characterised by AVMs. In the absence of functional Alk1, initial increases in endothelial cell number cause arteries nearest to the embryonic heart to become enlarged, increasing blood flow to downstream vessels, which then compensate by stabilising normally transient arteriovenous connections, consequently generating AVMs. The authors also found that alk1 expression requires blood flow, suggesting that the protein functions as a sensor of shear stress to limit vessel size. These results provide insight into the etiology of HTT2-associated AVMs and open up new avenues for therapeutic intervention.
alk1 mutant zebrafish shed light on the etiology of AVMs
alk1 mutant zebrafish shed light on the etiology of AVMs. Dis Model Mech 1 May 2011; 4 (3): 278. doi:
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