ArticleCirculation2024
HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.
Open access · greenAbstract read
In one paragraph
Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
7.7field-weighted citation impact, top 2% of its field
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
35 citing papers in PubMed, 50 citations in OpenAlex.
- Low-Intensity Ultrasound-Triggered Microbubble Cavitation Attenuates Diabetic Kidney Injury Partially by Reversing Endothelial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow.Journal of proteome research · 2026Article
- Time series analysis reveals the effect of shear stress profile on endothelial gene expression.BMC cardiovascular disorders · 2026Article
- Exercise-Induced Shear Stress, Endothelial Glycocalyx Remodeling, and Atherosclerotic Plaque Stability: A Mechanistic Review.Journal of cardiovascular development and disease · 2026Review
- Low Shear Stress Promotes Atherosclerosis by Mediating Pathological Accumulation of Endothelial Lipid Droplets via the KLF4/TFEB/ATP1A1 Axis.Journal of cardiovascular development and disease · 2026Article
- PDK4 drives abdominal aortic aneurysm by promoting smooth muscle cell metabolic reprogramming and NLRP3-mediated pyroptosis.Nature communications · 2026Article
- The Notch1 intracellular domain orchestrates mechanotransduction of fluid shear stress.Life science alliance · 2026Article
- Atherosclerotic plaque-derived extracellular vesicles mediate smooth muscle cell phenotypic switching and promote vascular remodeling : EVs promote VSMC phenotypic switching.Cellular and molecular life sciences : CMLS · 2026Article
- Role of Caveolae and Caveolin in Vascular Physiology and Pathology.Journal of the American Heart Association · 2026Review
- Endothelial senescence of the vertebral artery in the context of cervical degeneration: biomechanically driven remodeling of the hemodynamic environment.Frontiers in cell and developmental biology · 2026Review
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
- TNFSF13 Drives Atherosclerosis Progression by Targeting Macrophage Senescence.International journal of medical sciences · 2026Article
- Endothelial BMP6 Drives Hemodynamic-Dependent VSMCs Calcification in Carotid Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MAP3K3 Contributes to Myocardial Ischemia/Reperfusion Injury by Promoting Myeloid Cell Diapedesis through TAL1/JAM-A Pathway.Theranostics · 2026Article
- Disturbed flow induces reprogramming of endothelial cells to immune-like and foam cells under hypercholesterolaemia during atherogenesis.Cardiovascular research · 2025Article
- Decoding the Kruppel-like Transcription Factors in Atherosclerosis: Insight from Molecular and Translational Perspectives.International journal of molecular sciences · 2025Review
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Microfluidic Device Type Improves Heart mRNA DeliveryLangmuir : the ACS journal of surfaces and colloids · 2025Article
- HEG1 promotes gastric cancer progression by stabilizing AKT1 and is functionally regulated by the deubiquitinase USP48.European journal of medical research · 2025Article
Corrections and comments
- Commented on by
Authors and funding
19 authors at 4 institutions in 3 countries.
Ian A Tamargo *Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Kyung In Baek *Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Chenbo XuWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Dong Won KangWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Yerin KimWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0000-0003-2121-8511
Aitor AnduezaWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0000-0002-6501-3035
Darian WilliamsWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Catherine DemosWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Nicolas Villa-RoelWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0000-0002-2981-9330
Sandeep KumarWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0000-0003-3440-3628
Christian ParkWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Rachel ChoiWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0009-0001-6075-8687
Janie JohnsonWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Seowon ChangWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Paul KimWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0009-0000-9042-7996
Sheryl TanWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Kiyoung JeongWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).
Shoutaro TsujiMedical Technology & Clinical Engineering, Gunma University of Health and Welfare, Maebashi, Japan (S.T.).
Hanjoong JoWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (I.A.T., K.I.B., C.X., D.W.K., Y.K., A.A., D.W., C.D., N.V.-R., S.K., C.P., R.C., J.J., S.C., P.K., S.T., K.J., H.J.).ORCID 0000-0003-1833-372X
Norwegian Womens Public Health Association · NOEmory University · USThe Wallace H. Coulter Department of Biomedical Engineering · USGunma University of Health and Welfare · JP
Funding
Research Trainng in Academic CardiologyT32HL007745 · NHLBI · EMORY UNIVERSITY · PI TAYLOR, WILLIAM ROBERT · 1994 to 2023
$10.6MResearch Training Program Plan on Cell and Tissue Engineering (CTEng)T32GM008433 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI GARCIA, ANDRES J · 1991 to 2021
$7.1MMedical Scientist Training ProgramT32GM142617 · NIGMS · EMORY UNIVERSITY · PI Jason Yustein · 2022 to 2026
$7.0MGraduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1MShear stress, endothelial miRNAs, and AV calcificationR01HL119798 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2013 to 2022
$4.7MRole of CEBPb in flow-dependent endothelial dysfunction and atherosclerosisR01HL168383 · NHLBI · EMORY UNIVERSITY · PI Hanjoong Jo · 2023 to 2026
$3.0MHEG1 in endothelial function and atherosclerosisR01HL158571 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2021 to 2024
$2.7MRole of flow-sensitive KLK10 in endothelial dysfunction and atherosclerosisR01HL139757 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2018 to 2021
$1.6MCBT@EmTech - CardioVascular Biomechanics Training Program at Emory and GaTechT32HL166146 · NHLBI · EMORY UNIVERSITY · PI Lakshmi Prasad Dasi, Hanjoong Jo · 2023 to 2026
$1.3MRole of KLK10 in Endothelial Biology and AtherosclerosisF31HL145974 · NHLBI · EMORY UNIVERSITY · PI WILLIAMS, DARIAN · 2019 to 2021
$134kRole of Shear-Sensitive Protein HEG1 in Endothelial Biology and AtherosclerosisF31HL149285 · NHLBI · EMORY UNIVERSITY · PI TAMARGO, IAN A. · 2020 to 2022
$116kIntegration of advanced imaging and multiOMICs to elucidate pro-atherogenic effects of endothelial-to-Immune cell-like transition (EndICLT)F32HL167625 · NHLBI · EMORY UNIVERSITY · PI BAEK, KYUNG IN · 2023 to 2023
$74kNHLBI NIH HHS F31 HL145974NHLBI NIH HHS F31 HL149285NHLBI NIH HHS F32 HL167625NHLBI NIH HHS HL151358NHLBI NIH HHS R01 HL119798NHLBI NIH HHS R01 HL139757NHLBI NIH HHS R01 HL158571NHLBI NIH HHS R01 HL168383NHLBI NIH HHS T32 HL007745NHLBI NIH HHS T32 HL166146NIGMS NIH HHS T32 GM008433NIGMS NIH HHS T32 GM008602NIGMS NIH HHS T32 GM142617
Abstract
backgroundAtherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms.
methodsOur single-cell RNA-sequencing data using the mouse partial carotid ligation model was reanalyzed, which identified Heart-of-glass 1 (HEG1) as an s-flow-induced gene. HEG1 expression was studied by immunostaining, quantitive polymerase chain reaction, hybridization chain reaction, and Western blot in mouse arteries, human aortic endothelial cells (HAECs), and human coronary arteries. A small interfering RNA-mediated knockdown of HEG1 was used to study its function and signaling mechanisms in HAECs under various flow conditions using a cone-and-plate shear device. We generated endothelial-targeted, tamoxifen-inducible HEG1 knockout (HEG1
resultsS-flow induced HEG1 expression at the mRNA and protein levels in vivo and in vitro. S-flow stimulated HEG1 protein translocation to the downstream side of HAECs and release into the media, followed by increased messenger RNA and protein expression. HEG1 knockdown prevented s-flow-induced endothelial responses, including monocyte adhesion, permeability, and migration. Mechanistically, HEG1 knockdown prevented s-flow-induced KLF2/4 (Kruppel-like factor 2/4) expression by regulating its intracellular binding partner KRIT1 (Krev interaction trapped protein 1) and the MEKK3-MEK5-ERK5-MEF2 pathway in HAECs. Compared with littermate controls, HEG1
conclusionsOur findings indicate that HEG1 is a novel mediator of atheroprotective endothelial responses to flow and a potential therapeutic target.
Indexed as
AtherosclerosisHypercholesterolemiaPlaque, AtheroscleroticAnimalsEndothelial CellsFemaleHumansKruppel-Like Transcription FactorsMaleMembrane ProteinsMiceProprotein Convertase 9Transcription FactorsHEG1 protein, humanKLF2 protein, humanKruppel-Like Transcription FactorsMembrane ProteinsPCSK9 protein, humanProprotein Convertase 9Transcription Factorsatherosclerosisendothelial cellsheart-of-glass 1KLF2/4mechanobiology
Identifiers
What OpenQuestion holds
Texttitle and abstract
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.