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Identifier

000381552

Title

Migration and proliferation of endothelial cells

Alternative Title

Μελέτη μετανάστευσης και πολλαπλασιασμού των ενδοθηλιακών κυττάρων

Author

Νασίκας, Δημήτριος

Thesis advisor

Μπούμπας, Δημήτριος

Reviewer

Καρδάσης, Δημήτριος

Reviewer

Σανούδου, Δέσποινα

Abstract

Vascular ECs organize themselves in a single cellular layer, that is, the endothelium, at the luminal face of all blood vessels. In addition to its major function in controlling gas exchanges at the pulmonary level, the endothelium regulates the flow of circulating blood cells and of various bioactive molecules such as growth factors, coagulation proteins, lipoproteins and hormones, in particular through the presence of membrane-bound receptors. The endothelium also plays pivotal roles in the regulation of a broad range of physiological processes: it regulates hemostasis through the expression of both anti-thrombotic and prothrombotic factors; in tight cooperation with the underlying extracellular matrix and smooth muscle cells, it controls vascular tone with angiotensin I conversion and bradykinin degradation, and contributes to the metabolism of vasoactive amines. It also participates in inflammatory and immune responses through surface antigens and adhesive mole- cules and through the synthesis of cytokines. Moreover ECs, which are in direct contact with plasma and cellular components of blood, are targets of many endogenous molecules and xenobiotics. Endothelial cells have an important role in inflammation since they facilitate the migration of inflammatory cells to the inflamed tissues. Importantly chronic inflammation has deleterious effects on vascular endothelium promoting premature and accelerated atherosclerosis which is not fully accounted by traditional atherosclerosis risk factors. In fact, patients with chronic inflammatory diseases such systemic lupus erythematous and inflammatory arthritides have a 2-3 fold increased risk for cardiovascular events which represents a major cause of morbidity and mortality in these diseases. Delineation of the mechanisms involved in the interaction between endothelial cells and inflammation in this context may facilitate efforts to alleviate the deleterious effects of inflammation on vascular beds. This master’s thesis has two parts. In the first part we outline the establishment of an easy and cost-effective method for isolation and culture of HUVECs to supply our future experiments on the effects of inflammation and lipids on endothelial physiology. Addition of sera from active lupus patients in these cells resulted in activation of mechanisms of cellular migration and proliferation. The second part concerns the study of gene expression of human arterial endothelial cells ABSTRACT OF DISSERTATION 4 after incubation with recombinant HDL, which contained apolipoprotein E3. We took advantage of data generated in Dr. Zannis Lab (Boston University, USA) and in collaboration with Dr. Sanoudou Lab (Uinersity of Athens, Greece) we performed the bioinformatic analysis and literature search for the genes identified. Following total RNA isolation and hybridization on microarrays, the bioinformatics analysis revealed changes in specific genes which could inform our experiments. More specifically 16 genes were found to be directly involved in the molecular mechanisms leading to cellular proliferation. Further experiments should be carried out to validate our finding as these genes could be promising therapeutic targets against atherosclerosis.

Language

English

Subject

Endothelial cells

Migration

Proliferation

Ενδοθηλιακά κύτταρα

Μετανάστευση

Πολλαπλασιασμός

Issue date

2013-04-16

Collection