ArticleScience translational medicine2016
Somatic activating mutations in Pik3ca cause sporadic venous malformations in mice and humans.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 185 citations in OpenAlex.
- Trial
- From Somatic Driver to Molecular Therapy in Retinal, Choroidal and Periocular Vascular Disease: Mosaicism, Targetable Pathways and Ocular Toxicity.International journal of molecular sciences · 2026Review
- Pulmonary Embolism as the Initial Presentation of Klippel-Trénaunay Syndrome.JACC. Case reports · 2026Article
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Review
- Review
- A human endothelial and adipose stem cell-based co-culture model for venous malformations.Angiogenesis · 2026Article
- Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions.Radiology and oncology · 2026Review
- Trp53 loss drives the neoplastic transformation of Pik3caH1047R-induced vascular malformation in a mouse model.PloS one · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Advances in genetics, signaling, and modeling of venous malformations.Frontiers in cardiovascular medicine · 2026Review
- Identification of pathological CD133+ endothelial cells in venous malformations.Frontiers in cardiovascular medicine · 2026Article
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- Ultra-deep targeted next-generation sequencing with peripheral blood in patients with vascular malformations: a cohort of 40 patients.Molecular biology reports · 2025Article
- Semaphorin 3A and 3F Promote Lumen Expansion in TIE2-Mutated Venous Malformation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Somatic Uniparental Disomy of PTEN in Endothelial Cells Causes Vascular Malformations in Patients with PTEN Hamartoma Tumor Syndrome.Cancer discovery · 2025Article
- Angiopoietin-TIE2 feedforward circuit promotes PIK3CA-driven venous malformations.Nature cardiovascular research · 2025Article
- Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.APL bioengineering · 2025Article
- EndothelialInternational journal of medical sciences · 2025Article
- Venous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development.International journal of biological sciences · 2025Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 4 institutions in 3 countries.
Funding
Abstract
Venous malformations (VMs) are painful and deforming vascular lesions composed of dilated vascular channels, which are present from birth. Mutations in the TEK gene, encoding the tyrosine kinase receptor TIE2, are found in about half of sporadic (nonfamilial) VMs, and the causes of the remaining cases are unknown. Sclerotherapy, widely accepted as first-line treatment, is not fully efficient, and targeted therapy for this disease remains underexplored. We have generated a mouse model that faithfully mirrors human VM through mosaic expression of Pik3ca(H1047R), a constitutively active mutant of the p110α isoform of phosphatidylinositol 3-kinase (PI3K), in the embryonic mesoderm. Endothelial expression of Pik3ca(H1047R)resulted in endothelial cell (EC) hyperproliferation, reduction in pericyte coverage of blood vessels, and decreased expression of arteriovenous specification markers. PI3K pathway inhibition with rapamycin normalized EC hyperproliferation and pericyte coverage in postnatal retinas and stimulated VM regression in vivo. In line with the mouse data, we also report the presence of activating PIK3CA mutations in human VMs, mutually exclusive with TEK mutations. Our data demonstrate a causal relationship between activating Pik3ca mutations and the genesis of VMs, provide a genetic model that faithfully mirrors the normal etiology and development of this human disease, and establish the basis for the use of PI3K-targeted therapies in VMs.
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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.