טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSzafranek Tal
SubjectStudy of Molecular Mechanisms Underlying Inter-Individual
Differences in the Development and Progression of
Vascular Diseases
DepartmentDepartment of Medicine
Supervisor Professor Andrew Peter Levy


Abstract

Vascular disease is the main cause of morbidity and mortality in Western civilization. Two factors, which have been reported to contribute to the inter‑individual variability in the development and progression of vascular diseases, are hypoxic induction of Vascular Endothelial Growth Factor (VEGF) in monocytes and haptoglobin (Hp) phenotype.

We sought to determine the biochemical and molecular mechanisms, which are responsible for the association of VEGF and Hp to various vascular diseases.

Our first objective was finding an alternative model system to replace the primary monocytes in the VEGF hypoxic induction study. We attempted to determine VEGF hypoxic induction levels in EBV‑transformed B‑lymphocytes, placental fibroblasts, and adult skin fibroblasts, and compare them to monocytes from the respective donors.

Our second objective was to study the effects of cellular activation by Hp and Hp-Hb complexes, focusing on the interaction between Hp-Hb complexes and their suggested receptor CD163. We sought to develop a functional assay, intended to determine the identity of the factors, which are released upon CD163-mediated cellular activation and cellular activation by Hp or Hp-Hb in general.

We have learned from epidemiological studies that hypoxic induction of VEGF and Hp phenotype contribute to inter-individual differences in the development and progression of vascular disorders. This work presents part of our efforts to elucidate the biochemical basis underlying these phenomena. This is the first necessary step for the development of new pharmaceutical and therapeutic approaches, intended to prevent vascular diseases or hinder their deterioration.