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Dissertation_PSangwung FINAL_.pdf (2.03 MB)

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Kruppel-Like Transcription Factors: Master Regulators of Vascular Endothelium

Sangwung, Panjamaporn
http://orcid.org/0000-0002-8145-7947
http://rave.ohiolink.edu/etdc/view?acc_num=case1499426148493334

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
Endothelial cells (ECs) are central determinants of vascular health. Dysfunction of ECs, characterized in part by reduced nitric oxide (NO) signaling, contributes to various cardiovascular diseases worldwide. Multiple lines of evidence support an essential role for KLF2 and KLF4 in endothelial cell biology. However, the precise in vivo role of both factors in orchestrating EC health and vascular hemostasis remains undetermined. The central hypotheses of this work are (i) KLF2 and KLF4 serve as vital transcriptional regulators that maintain endothelial health and vascular hemostasis in adult animal, and (ii) these factors govern endothelial hemoglobin subunit alpha (HBA) expression, which is critical to finetune NO diffusion from EC to vascular smooth muscle cells (SMC). In vivo studies using inducible-genetic deficiency of both endothelial KLF2 and KLF4 (double knockout; EC-DKO) in adult mice caused acute deterioration of vascular permeability and disruption of the coagulation system, leading to heart failure, stroke, and death within days upon gene deletion. Mechanistically, abrogation of both KLF2 and KLF4 profoundly altered the EC transcriptome, suggesting that these factors regulate a broad range of endothelial genes and thus determine EC homeostasis. Further, KLF2 and KLF4 transcriptionally regulated HBA gene expression in ECs. Collectively, this study identifies KLF2 and KLF4 as essential determinants of endothelial health and vascular homeostasis.
Mukesh Jain, MD (Advisor)
George Dubyak, PhD (Committee Chair)
Thomas Nosek, PhD (Committee Member)
Julian Stelzer, PhD (Committee Member)
Jonathan Smith, PhD (Committee Member)
149 p.
Physiology

Recommended Citations

Citations

  • Sangwung, P. (2017). Kruppel-Like Transcription Factors: Master Regulators of Vascular Endothelium [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1499426148493334

    APA Style (7th edition)

  • Sangwung, Panjamaporn. Kruppel-Like Transcription Factors: Master Regulators of Vascular Endothelium. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1499426148493334.

    MLA Style (8th edition)

  • Sangwung, Panjamaporn. "Kruppel-Like Transcription Factors: Master Regulators of Vascular Endothelium." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1499426148493334

    Chicago Manual of Style (17th edition)

case1499426148493334
373
© 2017, some rights reserved.Creative Commons License Kruppel-Like Transcription Factors: Master Regulators of Vascular Endothelium by Panjamaporn Sangwung is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.