ArticleDevelopment (Cambridge, England)2011
Interaction between alk1 and blood flow in the development of arteriovenous malformations.
Article in Development (Cambridge, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed, 206 citations in OpenAlex.
- Extracellular matrix remodeling and internal elastic lamina alterations in cerebral arteriovenous malformations: Insights into vascular wall biology.Neurosurgical review · 2026Review
- Gene-Specific Endothelial Programs Drive AVM Pathogenesis inArteriosclerosis, thrombosis, and vascular biology · 2026Article
- Regionally Distinct Modes of Intestinal-Systemic Vascular Connections in Developing Zebrafish.Journal of developmental biology · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Automated analysis of zebrafish vascular networks using the VISTA-Z pipeline.Scientific reports · 2026Article
- Integrated lumped parameter modeling of cardiac-vascular interaction with valve dynamics and ventricular pressure-volume.Frontiers in bioengineering and biotechnology · 2026Article
- Evaluating Animal Models of Arteriovenous Malformation and Intracerebral Aneurysm: A Mechanistic Approach.Stroke (Hoboken, N.J.) · 2025Review
- Characterizing the Microenvironment of Cerebral Arteriovenous Malformations to Test Novel Treatment Modalities.Brain sciences · 2025Review
- PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations.Circulation · 2025Article
- The Role of Somatic Mutation in Hereditary Hemorrhagic Telangiectasia Pathogenesis.Journal of clinical medicine · 2025Review
- Divergent endothelial mechanisms drive arteriovenous malformations in Alk1 and SMAD4 loss-of-function.bioRxiv : the preprint server for biology · 2025Article
- A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations.Cardiovascular research · 2024Article
- CXCR3-CXCL11 Signaling Restricts Angiogenesis and Promotes Pericyte Recruitment.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Somatic mutations in arteriovenous malformations in hereditary hemorrhagic telangiectasia support a bi-allelic two-hit mutation mechanism of pathogenesis.American journal of human genetics · 2024Article
- Akt is a mediator of artery specification during zebrafish development.Development (Cambridge, England) · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Article
- Shear stress and pathophysiological PI3K involvement in vascular malformations.The Journal of clinical investigation · 2024Review
- Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells.Cells · 2024Article
- Blood flow regulatesbioRxiv : the preprint server for biology · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFβ family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.