The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
KLF2 and KLF4 control endothelial identity and vascular integrity
Open accessAbstract
Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal.
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“Cells fated for the endothelial terminal state diverge at E10.5 activating regulators of angiogenesis, such as Tbx1 and Foxc2, as well as genes associated with blood flow-associated shear stress, including Klf2 and Klf4”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Sangwung et al., 2017
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“the endothelial cluster is enriched for mechanosensitive ion channels and transcription factors associated with flow-induced shear stress and angiogenesis, such as Piezo1/2, Klf2/4, Foxc2, and Tbx1”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Sangwung et al., 2017
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Cites
Finishing the euchromatic sequence of the human genome
International Human Genome Sequencing Consortium (2004) · Nature · doi:10.1038/nature03001 · Cited by 4,971
Phenotypic Heterogeneity of the Endothelium
Aird, W. C. (2007) · Circulation Research · doi:10.1161/01.res.0000255691.76142.4a · Cited by 1,824
Guidelines for the diagnosis and management of disseminated intravascular coagulation
Levi, M. M., Toh, C., Thachil, J. V., & Watson, H. G. (2009) · British Journal of Haematology · doi:10.1111/j.1365-2141.2009.07600.x · Cited by 1,116
Klf4 is a transcription factor required for establishing the barrier function of the skin
Segre, J. A., Bauer, C. R., & Fuchs, E. V. (1999) · Nature Genetics · doi:10.1038/11926 · Cited by 810
KLF2 Is a Novel Transcriptional Regulator of Endothelial Proinflammatory Activation
SenBanerjee, S., Lin, Z., Atkins, G. B., Greif, D. M., Rao, R. M., Kumar, A., Feinberg, M. W., Chen, Z., Simon, D. I., Luscinskas, F. W., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031132 · Cited by 734
Self-citationIntegration of flow-dependent endothelial phenotypes by Kruppel-like factor 2
Parmar, K. M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24787 · Cited by 710
Dekker, R. J., van Soest, S., Fontijn, R. D., Salamanca, S., de Groot, P. G., VanBavel, E., Pannekoek, H., & Horrevoets, A. J. G. (2002) · Blood · doi:10.1182/blood-2002-01-0046 · Cited by 694
Role of Krüppel-Like Transcription Factors in Endothelial Biology
Atkins, G. B., & Jain, M. K. (2007) · Circulation Research · doi:10.1161/01.res.0000267856.00713.0a · Cited by 422
Self-citationKruppel-like Factor 4 Regulates Endothelial Inflammation
Hamik, A., Lin, Z., Kumar, A., Balcells, M., Sinha, S., Katz, J. P., Feinberg, M. W., Gerszten, R. E., Edelman, E. R., & Jain, M. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700078200 · Cited by 391
Self-citationKruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function
Lin, Z., Kumar, A., SenBanerjee, S., Staniszewski, K. E., Parmar, K. M., Vaughan, D. E., Gimbrone, M. A., Balasubramanian, V., García‐Cardeña, G., & Jain, M. K. (2005) · Circulation Research · doi:10.1161/01.res.0000159707.05637.a1 · Cited by 385
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Augustin, H. G., & Koh, G. Y. (2017) · Science · doi:10.1126/science.aal2379 · Cited by 790
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A systems view of the vascular endothelium in health and disease
Augustin, H. G., & Koh, G. Y. (2024) · Cell · doi:10.1016/j.cell.2024.07.012 · Cited by 383
Flow-induced reprogramming of endothelial cells in atherosclerosis
Tamargo, I. A., Baek, K. I., Kim, Y., Park, C. J., & Jo, H. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00883-1 · Cited by 306
Self-citationAndueza, A., Kumar, S., Kim, J. Y., Kang, D. W., Mumme, H., Perez, J. I., Villa-Roel, N., & Jo, H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108491 · Cited by 245
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Metadata
- Authors
- Sangwung, P., Zhou, G., Nayak, L., Chan, E. R., Kumar, S., Kang, D.-W., Zhang, R., Liao, X., Lu, Y., Sugi, K., Fujioka, H., Shi, H., Lapping, S. D., Ghosh, C. C., Higgins, S. J., Parikh, S. M., Jo, H., & Jain, M. K.
- Affiliations
- Cardiovascular Institute Hospital (JP)
- University Hospitals of Cleveland (US)
- Case Western Reserve University (US)
- Georgia Institute of Technology (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- JCI Insight
- Published
- 2017-02-23
- Volume
- 2
- Issue
- 4
- Pages
- e91700-e91700
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5313061
- OpenAlex
- W2588645651
- Cited by
- 247
- References
- 33
- Citations by year
- 2026: 31 · 2025: 24 · 2024: 32 · 2023: 31 · 2022: 29 · 2021: 23 · 2020: 31 · 2019: 20 · 2018: 16 · 2017: 10
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (16POST31200017)
- Case Western Reserve University
- School of Medicine, Case Western Reserve University
- National Institutes of Health (12SDG12070077)
- National Heart, Lung, and Blood Institute (R01HL125275, R01HL110630, R01HL086548, K08HL121131, R01HL112486, R01HL119195, R01HL093234)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- KLF2, KLF4, vascular integrity, endothelial-specific knockout, endothelial transcriptome, endothelial barrier function, coagulation system, myocardial infarction, heart failure, stroke
- MeSH terms
- Kruppel-Like Factor 4, Animals, Blood Coagulation, Blood Coagulation Disorders, Capillary Permeability, Endothelium, Vascular, Gene Expression Regulation, Heart Failure, Myocardial Infarction, Mice, Knockout, Stroke, Mice, Kruppel-Like Transcription Factors
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