Molecular mechanisms of Endothelial-Mesenchymal Transition in coronary artery stenosis and cardiac fibrosis

Byambasuren Vanchin

    Research output: ThesisThesis fully internal (DIV)

    857 Downloads (Pure)

    Abstract

    Endothelial homeostasis plays crucial role in vascular health by preventing unwarranted thrombosis, inflammation and regulating vascular tone. Endothelial dysfunction is a culprit in the development of many cardiovascular pathologies. Hence, insight into the molecular mechanisms that underlie endothelial dysfunction might allow for the discovery of innovative drugable targets to reduce the cardiovascular disease burden.
    Adverse endothelial plasticity and its specialized form Endothelial-Mesenchymal transition (EndMT) contributes to the development of multiple cardiovascular diseases including atherosclerosis and cardiac fibrosis. The induction of mesenchymal gene expression is not only regulated by changes in transcription factor binding to the DNA, but also by the accessibility of the DNA to these transcription factors, which is tightly regulated by epigenetics. Epigenetic modifications, through changes in histone tail modifications and DNA methylation, facilitate the compaction and decompaction of the DNA, thereby orchestrating its accessibility to transcription factors. Furthermore, transcribed genes are not always translated into proteins, as non-coding RNAs might induce posttranscriptional inhibition.
    Endothelial-mesenchymal transition is a crucial component of atherosclerosis and cardiac fibrosis development and shown to be modulated by fluid shear stress. In this thesis, we show that endothelial-mesenchymal transition is regulated on multiple levels by MAPK7, EZH2 and microRNAs and found dysregulation of these factors in experimental models of intimal hyperplasia and in human coronary artery disease. We uncovered a number of pivotal regulators of EndMT that might have therapeutic potential to ameliorate intimal hyperplasia and cardiac fibrosis.
    Translated title of the contributionMoleculaire mechanismen van Endotheliale-Mesenchymale Transitie in coronair stenose en cardiale fibrose
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Harmsen, Marco, Supervisor
    • Krenning, Guido, Co-supervisor
    Award date26-Jun-2018
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-0756-2
    Electronic ISBNs978-94-034-0755-5
    Publication statusPublished - 2018

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