ArticleAngiogenesis2021
SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis.
Article in Angiogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Single-Nucleus Multi-Omic Atlas Maps Regulatory Architecture and Non-Coding Variant Effects across Adult Human Tissues.bioRxiv : the preprint server for biology · 2026Article
- Placental Malperfusion Is Associated With Adverse Outcomes in Congenital Heart Disease and With Genetic Variants in Placental Developmental Pathways.Journal of the American College of Cardiology · 2025Article
- Spatiotemporal gene expression and cellular dynamics of the developing human heart.Nature genetics · 2025Article
- scTrans: Sparse attention powers fast and accurate cell type annotation in single-cell RNA-seq data.PLoS computational biology · 2025Article
- Review
- Pathogenic SMAD6 variants in patients with idiopathic and complex congenital heart disease associated pulmonary arterial hypertension.NPJ genomic medicine · 2025Article
- Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications.American journal of human genetics · 2024Article
- P300 Modulates Endothelial Mechanotransduction of Fluid Shear Stress.Cellular and molecular bioengineering · 2024Article
- Endothelial Cell Flow-Mediated Quiescence Is Temporally Regulated and Utilizes the Cell Cycle Inhibitor p27.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.International journal of molecular sciences · 2024Article
- Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.medRxiv : the preprint server for health sciences · 2024Article
- Endothelial cell flow-mediated quiescence is temporally regulated and utilizes the cell cycle inhibitor p27.bioRxiv : the preprint server for biology · 2024Article
- The modes of angiogenesis: an updated perspective.Angiogenesis · 2023Article
- Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development.Development (Cambridge, England) · 2023Article
- miR-342-5p downstream to Notch enhances arterialization of endothelial cells in response to shear stress by repressing MYC.Molecular therapy. Nucleic acids · 2023Article
- The emerging role of endothelial cells in the pathogenesis of thoracic aortic aneurysm and dissection.European heart journal · 2023Article
- Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation.eLife · 2023Article
- Endothelial Cell SMAD6 Balances ACVRL1/Alk1 Function to Regulate Adherens Junctions and Hepatic Vascular Development.bioRxiv : the preprint server for biology · 2023Article
- Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells.Scientific reports · 2023Article
- Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals.Clinical epigenetics · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Fluid shear stress provided by blood flow instigates a transition from active blood vessel network expansion during development, to vascular homeostasis and quiescence that is important for mature blood vessel function. Here we show that SMAD6 is required for endothelial cell flow-mediated responses leading to maintenance of vascular homeostasis. Concomitant manipulation of the mechanosensor Notch1 pathway and SMAD6 expression levels revealed that SMAD6 functions downstream of ligand-induced Notch signaling and transcription regulation. Mechanistically, full-length SMAD6 protein was needed to rescue Notch loss-induced flow misalignment. Endothelial cells depleted for SMAD6 had defective barrier function accompanied by upregulation of proliferation-associated genes and down regulation of junction-associated genes. The vascular protocadherin PCDH12 was upregulated by SMAD6 and required for proper flow-mediated endothelial cell alignment, placing it downstream of SMAD6. Thus, SMAD6 is a required transducer of flow-mediated signaling inputs downstream of Notch1 and upstream of PCDH12, as vessels transition from an angiogenic phenotype to maintenance of a homeostatic phenotype.
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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.