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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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.
“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
The Introduction (page unavailable) says KLF2 and KLF4 are enriched in endothelium and regulated by flow, supporting their association with blood-flow responses. It does not establish that endothelial-fated cells diverge at E10.5 or activate Klf2 and Klf4 at that stage, and it does not address Tbx1 or Foxc2. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe 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.
“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
The Introduction (page not specified) says KLF2 and KLF4 are enriched in the endothelium and regulated by flow. The paper does not support the citing sentence’s claims about Piezo1/2, Foxc2, Tbx1, or enrichment of those genes in the citing study’s endothelial cluster. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Finishing the euchromatic sequence of the human genome
International Human Genome Sequencing Consortium (2004) · Nature · doi:10.1038/nature03001 · Cited by 4,971 · see citing works
Phenotypic Heterogeneity of the Endothelium
Aird, W. C. (2007) · Circulation Research · doi:10.1161/01.res.0000255691.76142.4a · Cited by 1,744 · see citing works
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 · see citing works
Klf4 is a transcription factor required for establishing the barrier function of the skin
Segre, J. A., Bauer, C., & Fuchs, E. V. (1999) · Nature Genetics · doi:10.1038/11926 · Cited by 793 · see citing works
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 724 · see citing works
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 705 · see citing works
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 · see citing works
Role of Kruppel-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 414 · see citing works
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 · see citing works
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 379 · see citing works
Self-citationKuo, C. T., Veselits, M., Barton, K., Lu, M. M., Clendenin, C. J., & Leiden, J. M. (1997) · Genes & Development · doi:10.1101/gad.11.22.2996 · Cited by 369 · see citing works
Evolutionary origins of the blood vascular system and endothelium
Monahan-Earley, R. A., Dvořàk, A. M., & Aird, W. C. (2013) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12253 · Cited by 277 · see citing works
Endothelium as an organ system
Aird, W. C. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000129669.21649.40 · Cited by 260 · see citing works
A Stable Lead by Modification of Sato's Method
Hanaichi, T., Sato, T., IWAMOTO, T., Malavasi, J. Y., Hoshino, M., & Mizuno, N. (1986) · Journal of Electron Microscopy · doi:10.1093/oxfordjournals.jmicro.a050582 · Cited by 256 · see citing works
Healy, A. M., Rayburn, H., ROSENBERG, R. D., & Weiler-Guettler, H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.3.850 · Cited by 241 · see citing works
Angiopoietin-2 Causes Inflammation in Vivo by Promoting Vascular Leakage
Roviezzo, F., Tsigkos, S., Kotanidou, A. N., Bucci, M., Brancaleone, V., Cirino, G., & Papapetropoulos, A. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.086553 · Cited by 221 · see citing works
Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice
Zhou, G., Hamik, A., Nayak, L. V., Tian, H., Shi, H., Lu, Y., Sharma, N., Liao, X., Hale, A. T., Boerboom, L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci66056 · Cited by 217 · see citing works
Self-citationIsolation of endothelial cells from fresh tissues
B, J. R. V. B., Rousch, M., Castermans, K., van der Linden, E. P. M., & Griffioen, A. W. (2008) · Nature Protocols · doi:10.1038/nprot.2008.71 · Cited by 188 · see citing works
Angiopoietin-2 Is Critical for Cytokine-Induced Vascular Leakage
Benest, A. V., Kruse, K., Savant, S., Thomas, M., Laib, A. M., Loos, E. K., Fiedler, U., & Augustin, H. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070459 · Cited by 178 · see citing works
Heterogeneity of Endothelial Cells from Different Organ Sites in T-Cell Subset Recruitment
Lim, Y.-C., García‐Cardeña, G., Allport, J. R., Zervoglos, M., Connolly, A. J., Gimbrone, M. A., & Luscinskas, F. W. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64293-9 · Cited by 145 · see citing works
Isermann, B., Hendrickson, S. B., Zogg, M., Wing, M., Cummiskey, M., Kisanuki, Y. Y., Yanagisawa, M., & Weiler-Guettler, H. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13077 · Cited by 127 · see citing works
Kruppel-Like Factor 2 Regulates Endothelial Barrier Function
Lin, Z., Natesan, V., Shi, H., Dong, F., Kawanami, D., Mahabeleshwar, G. H., Atkins, G. B., Nayak, L. V., Cui, Y., Finigan, J. H., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.211474 · Cited by 126 · see citing works
Self-citationCowan, C. E., Kohler, E. E., Dugan, T. A., Mirza, K., Malik, A. B., & Wary, K. K. (2010) · Circulation Research · doi:10.1161/circresaha.110.219592 · Cited by 119 · see citing works
Disturbed-Flow-Mediated Vascular Reactive Oxygen Species Induce Endothelial Dysfunction
Heo, K., Fujiwara, K., & Abe, J. (2011) · Circulation Journal · doi:10.1253/circj.cj-11-1124 · Cited by 103 · see citing works
Basu, P., Morris, P. E., Haar, J. L., Wani, M. A., Lingrel, J. B., Gaensler, K. M. L., & Lloyd, J. A. (2005) · Blood · doi:10.1182/blood-2005-02-0674 · Cited by 99 · see citing works
Shi, H., Sheng, B., Zhang, F., Wu, C., Zhang, R., Zhu, J., Xu, K., Kuang, Y., Jameson, S. C., Lin, Z., et al. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00712.2012 · Cited by 91 · see citing works
Self-citationChiplunkar, A. R., Curtis, B. C., Eades, G. L., Kane, M. S., Fox, S., Haar, J. L., & Lloyd, J. A. (2013) · BMC Developmental Biology · doi:10.1186/1471-213x-13-40 · Cited by 80 · see citing works
Regulation of an Inflammatory Disease
Jain, M. K., Sangwung, P., & Hamik, A. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301925 · Cited by 70 · see citing works
Self-citationYoshida, T., Yamashita, M., Horimai, C., & Hayashi, M. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000622 · Cited by 55 · see citing works
Angiopoietin 2 Is a Potential Mediator of High-Dose Interleukin 2–Induced Vascular Leak
Gallagher, D. C., Bhatt, R. S., Parikh, S. M., Patel, P., Seery, V. J., McDermott, D. F., Atkins, M. B., & Sukhatme, V. P. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2509 · Cited by 52 · see citing works
Self-citationMitochondrial Division in Rat Cardiomyocytes: An Electron Microscope Study
Fujioka, H., Tandler, B., & Hoppel, C. L. (2012) · The Anatomical Record · doi:10.1002/ar.22523 · Cited by 51 · see citing works
Self-citationWeiler-Guettler, H., Aird, W. C., Husain, M., Rayburn, H., & ROSENBERG, R. D. (1996) · Circulation Research · doi:10.1161/01.res.78.2.180 · Cited by 51 · see citing works
Expression pattern of alternatively spliced PECAM‐1 isoforms in hematopoietic cells and platelets
Wang, Y., & Sheibani, N. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10321 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology
Augustin, H. G., & Koh, G. Y. (2017) · Science · doi:10.1126/science.aal2379 · Cited by 762 · see citing works
Basic and Therapeutic Aspects of Angiogenesis Updated
Eelen, G., Treps, L., Li, X., & Carmeliet, P. (2020) · Circulation Research · doi:10.1161/circresaha.120.316851 · Cited by 571 · see citing works
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 370 · see citing works
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 294 · see citing works
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 243 · see citing works
Self-citationSerine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells
Vandekeere, S., Dubois, C., Kalucka, J. M., Sullivan, M. R., García‐Caballero, M., Goveia, J., Chen, R., Diehl, F. F., Bar-Lev, L., Souffreau, J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.009 · Cited by 188 · see citing works
Self-citationTargeting Mechanosensitive Transcription Factors in Atherosclerosis
Niu, N., Xu, S., Xu, Y., Little, P. J., & Jin, Z. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.02.004 · Cited by 188 · see citing works
Miao, Y., Ajami, N. E., Huang, T.-S., Lin, F., Lou, C., Wang, Y., Li, S., Kang, J., Munkacsi, H., Maurya, M. R., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02113-y · Cited by 176 · see citing works
Krϋppel-like factors (KLFs) in renal physiology and disease
Rane, M. J., Zhao, Y., & Cai, L. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.021 · Cited by 179 · see citing works
Pharmacological basis and new insights of resveratrol action in the cardiovascular system
Cheng, C. K., Luo, J., Lau, C. W., Chen, Z., Tian, X. Y., & Huang, Y. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14801 · Cited by 159 · see citing works
Phenotypic diversity and metabolic specialization of renal endothelial cells
Dumas, S. J., Meta, E., Borri, M., Luo, Y., Li, X., Rabelink, T. J., & Carmeliet, P. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-021-00411-9 · Cited by 158 · see citing works
Zeng, H., Hou, Y., Zhou, X., Lang, L., Luo, H., Sun, Y., Wan, X., Yuan, T., Wang, R., Liu, Y., et al. (2022) · Theranostics · doi:10.7150/thno.74753 · Cited by 138 · see citing works
Maas, S. L., Soehnlein, O., & Viola, J. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02739 · Cited by 137 · see citing works
Systems biology analysis of longitudinal functional response of endothelial cells to shear stress
Ajami, N. E., Gupta, S., Maurya, M. R., Nguyen, P., Li, J. Y.-S., Shyy, J. Y.-J., Chen, Z., Chien, S., & Subramaniam, S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707517114 · Cited by 120 · see citing works
Ganta, V. C., Choi, M., Farber, C. R., & Annex, B. H. (2019) · Circulation · doi:10.1161/circulationaha.118.034165 · Cited by 123 · see citing works
Krüppel-like factors and vascular wall homeostasis
Fan, Y., Lu, H., Liang, W., Hu, W., Zhang, J., & Chen, Y. E. (2017) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjx037 · Cited by 120 · see citing works
Krüppel-Like Factors in Vascular Inflammation: Mechanistic Insights and Therapeutic Potential
Sweet, D. R., Fan, L., Hsieh, P. N., & Jain, M. K. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00006 · Cited by 110 · see citing works
Self-citationChakraborty, S., Singh, A., Wang, L. X., Wang, X., Sanborn, M. A., Ye, Z., Maienschein‐Cline, M., Mukhopadhyay, A., Ganesh, B. B., Malik, A. B., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20221388 · Cited by 111 · see citing works
VE-Cadherin Is Required for Lymphatic Valve Formation and Maintenance
Yang, Y., Cha, B., Motawe, Z. Y., Srinivasan, R. S., & Scallan, J. P. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.072 · Cited by 105 · see citing works
Chang, C., Liao, Y.-C., Huang, C., Lin, C.-M., Cheung, C. H. Y., Ruan, J., Yu, W.-H., Tsai, Y.-T., Lin, I.-J., Huang, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110016 · Cited by 106 · see citing works
Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations
Lopez‐Ramirez, M. A., Fonseca, G. J., Zeineddine, H. A., Girard, R., Moore, T., Pham, A., Cao, Y. J., Shenkar, R., de Kreuk, B.-J., Lagarrigue, F., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20171178 · Cited by 101 · see citing works
Maurya, M. R., Gupta, S., Li, J. Y.-S., Ajami, N. E., Chen, Z., Shyy, J. Y.-J., Chien, S., & Subramaniam, S. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023236118 · Cited by 100 · see citing works
The structure and function of YTHDF epitranscriptomic m6A readers
Sikorski, V., Selberg, S., Lalowski, M. M., Karelson, M. M., & Kankuri, E. M. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.03.004 · Cited by 99 · see citing works
Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension
Sindi, H. A., Russomanno, G., Satta, S., Abdul‐Salam, V. B., Jo, K. B., Qazi-Chaudhry, B., Ainscough, A. J., Szulcek, R., Bogaard, H. J., Morgan, C. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14966-x · Cited by 99 · see citing works
Non-canonical features of microRNAs: paradigms emerging from cardiovascular disease
Santovito, D., & Weber, C. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00680-2 · Cited by 94 · see citing works
Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease
Basu, M., Zhu, J., LaHaye, S., Majumdar, U., Jiao, K., Han, Z., & Garg, V. (2017) · JCI Insight · doi:10.1172/jci.insight.95085 · Cited by 91 · see citing works
Lotto, J., Drissler, S., Cullum, R., Wei, W., Setty, M., Bell, E. M., Boutet, S. C., Nowotschin, S., Kuo, Y.-Y., Garg, V., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.012 · Cited by 86 · see citing works
The MEK5/ERK5 Pathway in Health and Disease
Paudel, R., Fusi, L., & Schmidt, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147594 · Cited by 85 · see citing works
Cerebral cavernous malformations form an anticoagulant vascular domain in humans and mice
Lopez‐Ramirez, M. A., Pham, A., Girard, R., Wyseure, T. L., Hale, P., Yamashita, A., Koskimäki, J., Polster, S. P., Saadat, L., Romero, I. A., et al. (2018) · Blood · doi:10.1182/blood-2018-06-856062 · Cited by 83 · see citing works
Moonen, J.-R. A. J., Chappell, J., Shi, M., Shinohara, T., Li, D., Mumbach, M. R., Zhang, F., Nair, R. V., Nasser, J., Mai, D. H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32566-9 · Cited by 78 · see citing works
Maity, J., Deb, M., Greene, C. J., & Das, H. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101622 · Cited by 76 · see citing works
Cardiac Endothelial Cell Transcriptome
Lother, A., Bergemann, S., Deng, L., Moser, M., Bode, C., & Hein, L. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310549 · Cited by 73 · see citing works
He, M., Huang, T.-S., Li, S., Hong, H.-C., Chen, Z., Martin, M., Zhou, X., Huang, H., Su, S., Zhang, J., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.312301 · Cited by 69 · see citing works
Lu, Y. W., Martino, N., Gerlach, B. D., Lamar, J. M., Vincent, P. A., Adam, A. P., & Schwarz, J. J. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314978 · Cited by 71 · see citing works
Self-citationThe role of monocytosis and neutrophilia in atherosclerosis
Chistiakov, D. A., Grechko, A. V., Myasoedova, V. A., Melnichenko, A. А., & Orekhov, A. N. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13462 · Cited by 74 · see citing works
Zhang, X., Wang, L., Han, Z., Dong, J., Pang, D., Fu, Y., & Li, L. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01780-x · Cited by 69 · see citing works
Single-Cell Transcriptomics Reveals Endothelial Plasticity During Diabetic Atherogenesis
Zhao, G., Lu, H., Liu, Y., Zhao, Y., Zhu, T., Garcia-Barrio, M. T., Chen, Y. E., & Zhang, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.689469 · Cited by 67 · see citing works
Tamargo, I. A., Baek, K. I., Xu, C., Kang, D. W., Kim, Y., Andueza, A., Williams, D., Demos, C., Villa-Roel, N., Kumar, S., et al. (2023) · Circulation · doi:10.1161/circulationaha.123.064735 · Cited by 67 · see citing works
Self-citationA perfusable, vascularized kidney organoid-on-chip model
Kroll, K. T., Homan, K. A., Uzel, S. G. M., Mata, M. M., Wolf, K. J., Rubins, J. E., & Lewis, J. A. (2024) · Biofabrication · doi:10.1088/1758-5090/ad5ac0 · Cited by 63 · see citing works
Xu, Y., Xu, S., Liu, P., Koroleva, M., Zhang, S., Si, S., & Jin, Z. G. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.007134 · Cited by 63 · see citing works
Exploring the Role of Endothelial Cell Resilience in Cardiovascular Health and Disease
Gao, Y., & Galis, Z. S. (2021) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.120.314346 · Cited by 62 · see citing works
Wang, C., Dong, J., Sun, J., Huang, S.-K., Wu, F., Zhang, X., Pang, D., Fu, Y., & Li, L. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.06.025 · Cited by 59 · see citing works
Xu, S., Liu, Y.-J., Ding, Y., Luo, S.-H., Zheng, X.-Y., Wu, X., Liu, Z.-H., Ilyas, I., Chen, S., Han, S., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00690-5 · Cited by 56 · see citing works
Self-citationYang, H., Xi, X., Zhao, B., Su, Z., & Wang, Z. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.11.205 · Cited by 56 · see citing works
Atheroprone flow enhances the endothelial-to-mesenchymal transition
Lai, B., Li, Z., He, M., Wang, Y., Chen, L., Zhang, J., Yang, Y., & Shyy, J. Y.-J. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00213.2018 · Cited by 53 · see citing works
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
Hess, D. L., Kelly‐Goss, M. R., Cherepanova, O. A., Nguyen, A. T., Baylis, R. A., Tkachenko, S., Annex, B. H., Peirce, S. M., & Owens, G. K. (2019) · Nature Communications · doi:10.1038/s41467-019-08811-z · Cited by 52 · see citing works
Lee, O.-H., Woo, Y. M., Moon, S., Lee, J., Park, H., Jang, H. S., Park, Y., Bae, S., Park, K., Heo, J. H., et al. (2020) · Aging · doi:10.18632/aging.202176 · Cited by 52 · see citing works
Caradu, C., Couffinhal, T., Chapouly, C., Guimbal, S., Hollier, P.-L., Ducasse, É., Bura-Rivière, A., Dubois, M., Gadeau, A., & Renault, M. (2018) · Circulation Research · doi:10.1161/circresaha.118.313177 · Cited by 50 · see citing works
Qiao, S., Zhang, W., Yin, Y., Wei, Z., Chen, F., Zhao, J., Sun, X., Mu, D., Xie, J., & Xu, B. (2020) · Theranostics · doi:10.7150/thno.45459 · Cited by 50 · see citing works
Chemokine mediated signalling within arteries promotes vascular smooth muscle cell recruitment
Stratman, A. N., Burns, M. C., Farrelly, O. M., Davis, A. E., Li, W., Pham, V. N., Castranova, D., Yano, J. J., Goddard, L. M., Nguyen, O., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-01462-7 · Cited by 48 · see citing works
Lu, H., Yuan, P., Ma, X., Jiang, X., Liu, S., Ma, C., Philipsen, S., Zhang, Q., Yang, J., Xu, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36409-z · Cited by 45 · see citing works
Peghaire, C. R., Dufton, N., Lang, M., Salles‐Crawley, I. I., Ahnström, J., Kalna, V., Raimondi, C., Pericleous, C., Inuabasi, L., Kiseleva, R. Y., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12897-w · Cited by 45 · see citing works
Tajadura, V., Hansen, M. H., Smith, J., Charles, H., Rickman, M., Farrell‐Dillon, K., Claro, V., Warboys, C. M., & Ferro, A. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2687-6 · Cited by 45 · see citing works
Transcriptional Regulation of Osteoclastogenesis: The Emerging Role of KLF2
Rolph, D. N., & Das, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00937 · Cited by 44 · see citing works
Endothelial Cell Mechano-Metabolomic Coupling to Disease States in the Lung Microvasculature
Wu, D., & Birukov, K. G. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00172 · Cited by 42 · see citing works
Kotlyarov, S. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179770 · Cited by 42 · see citing works
Signalling through cerebral cavernous malformation protein networks
Su, V. L., & Calderwood, D. (2020) · Open Biology · doi:10.1098/rsob.200263 · Cited by 41 · see citing works
Tsaryk, R., Yucel, N. D., Leonard, E. V., Díaz, N., Bondareva, O., Odenthal-Schnittler, M., Arany, Z. P., Vaquerizas, J. M., Schnittler, H., & Siekmann, A. F. (2022) · Scientific Reports · doi:10.1038/s41598-022-08645-8 · Cited by 39 · see citing works
A review of KLF4 and inflammatory disease: Current status and future perspective
Liang, Y., Zhao, J., Dai, T., Li, X., Chen, L., He, Z.-X., Guo, M., Zhao, J., & Xu, L. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107345 · Cited by 39 · see citing works
Abello, J., Raghavan, S. A., Yien, Y. Y., & Stratman, A. N. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102404 · Cited by 38 · see citing works
Sarvestani, S. K., Signs, S. A., Lefebvre, V., Mack, S. C., Ni, Y., Morton, A. R., Chan, E. R., Li, X., Fox, P. L., Ting, A. H., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25617 · Cited by 38 · see citing works
Self-citationLong noncoding RNA LEENE promotes angiogenesis and ischemic recovery in diabetes models
Tang, X., Luo, Y., Yuan, D., Calandrelli, R., Malhi, N. K., Sriram, K., Miao, Y., Lou, C.-H., Tsark, W. M. K., Tapia, A., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci161759 · Cited by 38 · see citing works
Intimal Hyperplasia of Arteriovenous Fistula
Ma, S., Duan, S., Ya, L., & Wang, H. (2022) · Annals of Vascular Surgery · doi:10.1016/j.avsg.2022.04.030 · Cited by 37 · see citing works
Gómez-Salinero, J. M., Itkin, T., Houghton, S., Badwe, C. R., Lin, Y., Kalna, V., Dufton, N., Peghaire, C. R., Yokoyama, M., Wingo, M. E., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00128-3 · Cited by 37 · see citing works
Chen, F., Zhan, J., Liu, M., Mamun, A. A., Huang, S., Tao, Y., Zhao, J., Zhang, Y., Xu, Y., He, Z., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.85692 · Cited by 36 · see citing works
Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung
Bishop, C., Yan, K., Nguyen, W., Rawle, D. J., Tang, B., Larcher, T., & Suhrbier, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1382655 · Cited by 36 · see citing works
Li, H., Wang, Y., Liu, J., Chen, X., Duan, Y., Wang, X., Shen, Y., Kuang, Y., Zhuang, T., Tomlinson, B., et al. (2020) · Theranostics · doi:10.7150/thno.48153 · Cited by 36 · see citing works
Thakar, S., Katakia, Y. T., Ramakrishnan, S. K., Thakkar, N. P., & Majumder, S. (2021) · Cells · doi:10.3390/cells10102548 · Cited by 36 · see citing works
KLF4-Induced Connexin40 Expression Contributes to Arterial Endothelial Quiescence
Denis, J.-F., Diagbouga, M. R., Molica, F., Hautefort, A., Linnerz, T., Watanabe, M., Lemeille, S., Bertrand, J. Y., & Kwak, B. R. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00080 · Cited by 35 · see citing works
Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo
Yeh, C., Cheng, S.-F., Lin, Y.-S., Shentu, T., Huang, R., Zhu, J., Chen, Y.-T., Kumar, S., Lin, M., Kao, H., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl8096 · Cited by 35 · see citing works
Self-citationThe Atherosclerotic Plaque Microenvironment as a Therapeutic Target
Pandit, R., & Yurdagul, A. (2025) · Current Atherosclerosis Reports · doi:10.1007/s11883-025-01294-y · Cited by 33 · see citing works
Lu, Y. W., Lowery, A. M., Sun, L.-Y., Singer, H. A., Dai, G., Adam, A. P., Vincent, P. A., & Schwarz, J. J. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309180 · Cited by 33 · see citing works
Self-citationPost-translational modifications of S1PR1 and endothelial barrier regulation
Anwar, M., & Mehta, D. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158760 · Cited by 33 · see citing works
Tirone, M., Giovenzana, A., Vallone, A., Zordan, P., Sormani, M., Nicolosi, P. A., Meneveri, R., Gigliotti, C. R., Spinelli, A. E., Bocciardi, R., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01640 · Cited by 32 · see citing works
Caliceti, C., Malaguti, M., Marracino, L., Barbalace, M. C., Rizzo, P., & Hrelia, S. (2022) · Antioxidants · doi:10.3390/antiox11091786 · Cited by 35 · see citing works
Fan, Z., Ardicoglu, R., Batavia, A. A., Rust, R., von Ziegler, L., Waag, R., Zhang, J., Desgeorges, T., Sturman, O., Dang, H., et al. (2023) · Angiogenesis · doi:10.1007/s10456-023-09870-z · Cited by 33 · see citing works
microRNA-32-5p targets KLF2 to promote gastric cancer by activating PI3K/AKT signaling pathway.
Wang, Q., He, Y., Kan, W., Li, F., Ji, X., Wu, X., Wang, X., Zhang, Y., & Chen, J. (2019) · Europe PMC (PubMed Central) · Cited by 31 · see citing works
Well-Known and Novel Players in Endothelial Dysfunction: Updates on a Notch(ed) Landscape
Fortini, F., Sega, F. V. D., Marracino, L., Severi, P., Rapezzi, C., Rizzo, P., & Ferrari, R. (2021) · Biomedicines · doi:10.3390/biomedicines9080997 · Cited by 32 · see citing works
Pandey, D., Nomura, Y., Rossberg, M. C., Hori, D., Bhatta, A., Keceli, G., Leucker, T. M., Santhanam, L., Shimoda, L. A., Berkowitz, D. E., et al. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310660 · Cited by 31 · see citing works
Yang, Y., Mumau, M. D., Tober, J. M., Zhu, Q., Bennett, L. F., Hong, C. C., Sung, D. C., Keller, T. C. S., Uzun, Y., Gao, P., et al. (2022) · Blood · doi:10.1182/blood.2021013934 · Cited by 28 · see citing works
Stem cell-derived vessels-on-chip for cardiovascular disease modeling
Marder, M., Remmert, C., Perschel, J. A., Otgonbayar, M., von Toerne, C., Hauck, S. M., Bushe, J., Feuchtinger, A., Sheikh, B. N., Moussus, M., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114008 · Cited by 32 · see citing works
Saum, K. L., Campos, B., Celdran‐Bonafonte, D., Nayak, L. V., Sangwung, P., Thakar, C. V., Roy‐Chaudhury, P., & Owens, A. P. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.007566 · Cited by 30 · see citing works
Self-citationThe function of long non-coding RNAs in vascular biology and disease
Kok, F. O., & Baker, A. H. (2019) · Vascular Pharmacology · doi:10.1016/j.vph.2018.06.004 · Cited by 30 · see citing works
Dai, Y., Yan, T., & Gao, Y. (2020) · Diagnostic Pathology · doi:10.1186/s13000-020-00942-y · Cited by 30 · see citing works
Gao, C., Qian, H., Shi, Q., & Zhang, H. (2020) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-19-700 · Cited by 30 · see citing works
Přibyl, M., Hodný, Z., & Kubíková, I. (2021) · Genes · doi:10.3390/genes12010108 · Cited by 30 · see citing works
Linna-Kuosmanen, S., Schmauch, E., Galani, K., Ojanen, J., Boix, C. A., Örd, T., Toropainen, A., Singha, P., Moreau, P. R., Harju, K., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101556 · Cited by 27 · see citing works
Blazeski, A., Floryan, M. A., Zhang, Y., Fajardo‐Ramírez, Ó. R., Meibalan, E., Ortiz-Urbina, J., Angelidakis, E., Shelton, S. E., Kamm, R. D., & García‐Cardeña, G. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122686 · Cited by 26 · see citing works
Neonatal hyperoxia depletes pulmonary vein cardiomyocytes in adult mice via mitochondrial oxidation
Yee, M., Cohen, E. D., Domm, W., Porter, G. A., Jr., McDavid, A., & O’Reilly, M. A. (2018) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00409.2017 · Cited by 27 · see citing works
Huang, T., Yin, J., Ren, S., & Zhang, X. (2023) · Cytokine · doi:10.1016/j.cyto.2023.156288 · Cited by 26 · see citing works
Helle, E., Ampuja, M., Antola, L., & Kivelä, R. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.591450 · Cited by 25 · see citing works
Kant, S., Tran, K.-V., Kvandová, M., Caliz, A. D., Yoo, H.-J., Learnard, H., Dolan, A. C., Craige, S. M., Hall, J. D., Jiménez, J. M., et al. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.317066 · Cited by 24 · see citing works
Yang, K., Cui, S., Wang, J., Xu, T., Du, H., Yue, H., Ye, H., Guo, J., Zhang, J., Li, P., et al. (2023) · Advanced Science · doi:10.1002/advs.202302231 · Cited by 24 · see citing works
Regulation of endothelial hemoglobin alpha expression by Kruppel-like factors
Sangwung, P., Zhou, G., Lu, Y. F., Liao, X., Wang, B., Mutchler, S. M., Miller, M. P., Chance, M. R., Straub, A. C., & Jain, M. K. (2017) · Vascular Medicine · doi:10.1177/1358863x17722211 · Cited by 24 · see citing works
Self-citationZimmermann, M., Beer, L., Ullrich, R., Lukovic, D., Simader, E., Traxler, D., Wagner, T., Nemec, L., Altenburger, L. M., Zuckermann, A. O., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17955 · Cited by 22 · see citing works
Boriushkin, E., Zhang, H., Becker, M., Peachey, J., Shatat, M. A., Adams, R. H., & Hamik, A. (2019) · Angiogenesis · doi:10.1007/s10456-018-9657-y · Cited by 22 · see citing works
Sweet, D. R., Padmanabhan, R., Liao, X., Dashora, H. R., Tang, X., Nayak, L. V., Jain, R., Val, S. D., Vinayachandran, V., & Jain, M. K. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.121.024303 · Cited by 20 · see citing works
Self-citationSystemic Inflammation Causes Microglial Dysfunction With a Vascular AD phenotype
Bathini, P., Dupanloup, I., Zenaro, E., Terrabuio, E., Fischer, A., Ballabani, E., Doucey, M., & Alberi, L. A. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100568 · Cited by 20 · see citing works
Cho, D. I., Ahn, J. H., Kang, B. G., Hwang, I., Cho, H. H., Jun, J. H., Yoo, J. Y., Cho, M., Yoo, S. J., Kim, H.-S., et al. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.125.322700 · Cited by 21 · see citing works
Demos, C., Johnson, J., Andueza, A., Park, C. J., Kim, Y., Villa-Roel, N., Kang, D. W., Kumar, S., & Jo, H. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.979745 · Cited by 19 · see citing works
Self-citation
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
