Studies on the mechanism of fluorene induce angiogenesis in human umbilical vein endothelial cells
| Autor: | Shih-Hsin Chiu, 邱世昕 |
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| Rok vydání: | 2007 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 95 Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants which have been found in the exhausts of industrial manufacture and motor vehicles, tobacco smoke, and contaminated food and water due to improper cooking. In previous studies, PAHs are potently carcinogenic and immunotoxic, and they have also been suggested to be involved in cardiovascular dysfunction. Angiogenesis, the formation of new blood vessels from pre-existing endothelium, plays a critical role in a variety of physiological and pathological conditions including wound healing, embryonic development, female reproductive cycle, diabetic retinopathy, tumor growth, metastasis and various chronic inflammation disorders. We recently found that PAHs induced eNOS protein expression in HUVECs, and increased eNOS protein activity and NO production. They also affected the homeostasis of intracellular calcium concentration and induced cell adhesion molecules expression. In addition, NO, calcium and adhesion molecules mediate the processes of angiogenesis. Thus, we chose fluorene, one of PAHs which contain three bezene rings, to study the effect of PAHs on angiogenesis in HUVECs. The process of angiogenesis is complex and involves several discrete steps, such as extracellular matrix degradation, cell adhesion, proliferation, migration, and morphological differentiation of endothelial cells to form tubes. In this study, we found that fluorene induced angiogenic effects by cell adhesion, cell migration, and tube formation assays. In addition, we also found that fluorene increased integrin αvβ3 protein expression by transcription. The angiogenic effect induced by fluorene may be via the expression of integrin αvβ3 because cell adhesion, migration, and tube formation were inhibited by anti-integrin αvβ3 antibody (LM609) treatment. Fluorene elicited angiogenic effects in in vitro angiogenesis assays, and incubation of HUVECs with fluorene induced integrin αvβ3 expression; these effects were inhibited by phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) and antioxidant (NAC). These findings suggested that fluorene induced vascular endothelial cell adhesion, migration, and tube formation via increasing integrin αvβ3 expression, and ROS and PI3K/Akt signaling pathway involved in angiogenesis activated by fluorene were also established. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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