ReviewThe Journal of clinical investigation2024
Shear stress and pathophysiological PI3K involvement in vascular malformations.
Review in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed.
- Loss of Smad4 drives vascular malformations via c-KIT-dependent high-fluid shear stress mimicry.The Journal of clinical investigation · 2026Article
- Gene-Specific Endothelial Programs Drive AVM Pathogenesis inArteriosclerosis, thrombosis, and vascular biology · 2026Article
- Article
- Protocol for PI3K inhibitor-free differentiation and maturation of human iPSC-derived arterial- and venous-like endothelial cells.STAR protocols · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Mechanical preconditioning by shear stress enhances memory formation and anti-tumor function of CAR-T cells.Cancer immunology, immunotherapy : CII · 2026Article
- Mechanochemical regulation of organoid morphogenesis: Integrated signaling circuits in engineered microenvironments.Materials today. Bio · 2026Review
- Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in Gαq-R183Q-driven capillary malformations.Angiogenesis · 2026Article
- Mapping the global clinical trial landscape of targeted therapy for vascular malformations.International journal of surgery (London, England) · 2026Article
- Metabolic Syndrome-Driven Changes in Cardiac Lymphatic Endothelium: mRNA Expression and Emerging Questions.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Flow-induced Klf4-Akt signaling links EC cycling to mural cell defects in arterial-venous malformations.Theranostics · 2026Article
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- Physiological fluid shear stress synergistically enhances the protective effects of Salvia miltiorrhiza extract on endothelial cells.Scientific reports · 2025Article
- Multidimensional optimization of stent design for endothelial shear stress regulation: Geometric structuring, surface functionalization strategies to mitigate thrombosis and restenosis.International journal of cardiology. Heart & vasculature · 2025Review
- Interleukin-33-Mediated Mechanical-Loading Induced Degeneration of Knee Joint Chondrocytes.FASEB bioAdvances · 2025Article
- Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies.Biomolecules · 2025Review
- Mapping the Nitric Oxide Axis in IVF: Genotype Associations in Antagonist Cycles.International journal of molecular sciences · 2025Article
- A Rare Intra-Atrial Cyst of Vascular Origin: Genetic Insights From a Case.JACC. Case reports · 2025Article
- Common and distinct circulating microRNAs in four neurovascular disorders.Biochemistry and biophysics reports · 2025Article
- Normal stress on surface of mesenchymal stem cells boosts extracellular vesicle secretion and regenerative bioactivity.Journal of nanobiotechnology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Molecular characterization of vascular anomalies has revealed that affected endothelial cells (ECs) harbor gain-of-function (GOF) mutations in the gene encoding the catalytic α subunit of PI3Kα (PIK3CA). These PIK3CA mutations are known to cause solid cancers when occurring in other tissues. PIK3CA-related vascular anomalies, or "PIKopathies," range from simple, i.e., restricted to a particular form of malformation, to complex, i.e., presenting with a range of hyperplasia phenotypes, including the PIK3CA-related overgrowth spectrum. Interestingly, development of PIKopathies is affected by fluid shear stress (FSS), a physiological stimulus caused by blood or lymph flow. These findings implicate PI3K in mediating physiological EC responses to FSS conditions characteristic of lymphatic and capillary vessel beds. Consistent with this hypothesis, increased PI3K signaling also contributes to cerebral cavernous malformations, a vascular disorder that affects low-perfused brain venous capillaries. Because the GOF activity of PI3K and its signaling partners are excellent drug targets, understanding PIK3CA's role in the development of vascular anomalies may inform therapeutic strategies to normalize EC responses in the diseased state. This Review focuses on PIK3CA's role in mediating EC responses to FSS and discusses current understanding of PIK3CA dysregulation in a range of vascular anomalies that particularly affect low-perfused regions of the vasculature. We also discuss recent surprising findings linking increased PI3K signaling to fast-flow arteriovenous malformations in hereditary hemorrhagic telangiectasias.
Indexed as
Identifiers
What Socratic 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 Socratic graph.