Thesis supervisor: Viktória Jeney
Location of studies (in Hungarian): University of Debrecen Abbreviation of location of studies: DEÁOK
Description of the research topic:
Once considered as a passive process, nowadays it is evident that vascular calcification is an active cell-mediated process. Vascular calcification now is considered as a consequence of osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs). During this differentiation process VSMCs lose their linage markers and gain osteoblast-like phenotype. This is orchestrated mainly by the master osteogenic transcription factors RUNX2 that control the transcription of different osteoblast-like proteins. Different triggers of such osteogenic trans-differentiation have been identified including but not limited to elevated inorganic phosphate that can play a pathophysiologic role in accelerated mineralization in patients with chronic kidney disease, and high glucose which is linked to increased mineralization in patients with type 2 diabetes. It is not clear whether other cells are involved in vascular calcification, but recently a population of macrophages with high expression of osteoblast-specific markers was identified in peripheral blood of patients with type2 diabetes.
Under this project we will address whether macrophages undergo osteogenic differentiation in response to different osteogenic stimuli such as high inorganic phosphate or high glucose. We will use the murine macrophage cell line as well as primary macrophages from bone-marrow and peripheral blood. We will determine mRNA and protein expressions of certain osteoblast-specific markers, such as RUNX2, SOX9, alkaline phosphatase, osteocalcin, etc. We will also measure matrix mineralization. To investigate whether macrophages are involved in atherosclerosis-associated intima calcification, we will use ApoE deficient mice model, in which atherosclerotic plaque formation can be triggered by high-cholesterol diet. Macrophage-targeted deletion of Runx2 will help us to investigate the specific involvement of macrophages in plaque calcifi
Number of students who can be accepted: 1
Deadline for application: 2019-01-31
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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