Abstract
Arteriovenous malformations are a vascular anomaly typically present at birth, characterized by an abnormal connection between an artery and a vein (bypassing the capillaries). These high flow lesions can vary in size and location. Therapeutic approaches are limited, and AVMs can cause significant morbidity and mortality. Here, we describe our current understanding of the pathogenesis of arteriovenous malformations based on preclinical and clinical findings. We discuss past and present accomplishments and challenges in the field and identify research gaps that need to be filled for the successful development of therapeutic strategies in the future.
Highlights
Arteriovenous malformations (AVMs) are abnormal shunts between arteries and veins that bypass the capillary bed
It is inherited in an autosomal dominant fashion due to loss of function variants in two genes [RAS P21 Protein Activator 1 (RASA1) and Ephrin Receptor B4 (EPHB4)]
Even a complete loss of protein alone was not sufficient for AVMs to grow in these mice. These studies suggested that a combination of a loss of one functional allele in an hemorrhagic telangiectasia (HHT)-locus, a local loss of protein, and an angiogenic stimulus directed towards endothelial cell (EC) might be required for AVM development in mice
Summary
Arteriovenous malformations (AVMs) are abnormal shunts between arteries and veins that bypass the capillary bed. Complications arising from these direct arteriovenous communications are dependent on their anatomical location and stage of development and include stroke, brain abscess, hypoxemia, or local rupture with hemorrhages that can be lifethreatening [1,2,3]. Mounting evidence suggests that even for familial AVMs, underlying genetic defects in the germline alone might not be sufficient for AVMs to manifest Local events such as somatic mutations and pro-angiogenic stimuli might be required drivers [9,10,11,12,13]. We highlight the genetics, natural history, diagnosis, histopathology, preclinical model systems, and altered pathways, as well as promising medical approaches targeting relevant pathways for AVMs
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