dc.contributor.author |
Azrak, Zeina Mhd Hazem, |
dc.date.accessioned |
2017-08-30T14:12:28Z |
dc.date.available |
2017-08-30T14:12:28Z |
dc.date.issued |
2015 |
dc.date.submitted |
2015 |
dc.identifier.other |
b18392076 |
dc.identifier.uri |
http://hdl.handle.net/10938/10796 |
dc.description |
Thesis. M.Sc. American University of Beirut. Department of Pharmacology and Toxicology. Faculty of Medicine 2015. W 4 A997i 2015 |
dc.description |
Advisor: Dr. Ramzi Sabra, Professor, Department of Pharmacology and Toxicology ; Co-Advisor: Dr. Asad Zeidan, Assistant Professor, Department of Anatomy, Cell Biology and Physiological Sciences ; Committee members: Dr. Joseph Simaan, Professor, Department of Pharmacology and Toxicology ; Dr. Ali Eid, Assistant Professor, Department of Pharmacology and Toxicology. |
dc.description |
Includes bibliographical references (leaves 92-115) |
dc.description.abstract |
Background and aims: There is considerable evidence supporting the role of Ang II and the obesity-associated adipokine leptin, in the pathogenesis of vascular hypertrophy and remodeling. Both proteins appear to mediate the hypertrophic effect of one another, possibly through a crosstalk or feedback mechanism. The correlation between Ang II and leptin has been scarcely investigated. In this study, we aimed to investigate whether Ang II induced leptin synthesis in vascular smooth muscle cells (VSMCs), to define the molecular mechanisms and pathways underlying this process; and to explore the particular molecular mechanisms that mediate the Ang II-induced hypertrophy and link them to leptin synthesis. Finally, we explored the role of the anti-atherosclerotic adipokine, adiponectin, in inhibiting the Ang II-induced vascular remodeling and hypertrophy. Methods: A VSMC cell culture and RPV (Rat Portal Vein) organ culture was performed in the absence-presence of Ang II; some studies involved the pretreatment of VSMCs and RPVs (before adding Ang II) with an inhibitor or with adiponectin. Western blot analysis was performed to detect Ang II-induced leptin, p-cofilin, p-p38, p-Akt and p-ERK1-2 expression. The effect of Ang II on ROS (Reactive Oxygen Species) formation and the G-F actin (Globular-Filamentous actin) ratio was detected by immunohistochemical analysis (via laser confocal microscopy) on VSMCs of the rat aorta. The actin depolymerization agent cytochalasin D (CD) and the RhoA-ROCK pathway inhibitor y-27632, the NOX inhibitor apocynin and the EGFR (Epidermal Growth Factor receptor) inhibitor AG-1478, were used to investigate the involvement of the intact actin cytoskeleton, the RhoA-ROCK pathway, NOX and EGFR activation respectively. Immunocytochemical analysis (via laser confocal microscopy) was done to study both, the effect of Ang II on leptin synthesis and the GATA-4 nuclear translocation in the VSMCs. The mRNA expressions of AdipoR1, AdipoR2 and adiponectin were deduced by qPCR analysis. Results: We were a |
dc.format.extent |
1 online resource ( 115 leaves) |
dc.language.iso |
eng |
dc.relation.ispartof |
Theses, Dissertations, and Projects |
dc.subject.classification |
W 4 A997i 2015 |
dc.subject.lcsh |
Dissertations, Academic. |
dc.subject.lcsh |
Angiotensin. |
dc.subject.lcsh |
Hypertension. |
dc.subject.lcsh |
Leptin. |
dc.title |
Investigating the molecular mechanisms of Angiotensin II-induced leptin synthesis in vascular smooth muscle cells - |
dc.type |
Thesis |
dc.contributor.department |
Department of Pharmacology and Toxicology,Faculty of Medicine, |
dc.contributor.institution |
American University of Beirut. |