Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/10389
Differential regulation of Adamts-1 gene expression by VEGF and Angiotensin-II in endothelial and vascular smooth muscle cells
18th International Vascular Biology Meeting. 2014
Vascular remodeling consists of the structural alteration and arrangement of blood vessels. During this process cell migration, proliferation, cell death, and modifications in extracellular matrix (ECM) components are produced. It is present in major vascular diseases such as hypertension, aneurysm, vascular stenosis, and atherosclerosis. Vascular Endothelial Growth Factor (VEGF) and Angiotensin- II (Ang-II) major regulatory factors in vascular biology. VEGF induce endothelial cell migration and proliferation and contribute to pathophysiological angiogenesis. Ang-II is a potent vasoconstrictor agent, although it is also involved in inflammation, cell growth, vascular permeability and matrix deposition. In vivo, Ang-II administration induces aortic abdominal aneurysm (AAA) in ApoE KO mice, and increases restenosis and atherosclerosis. These processes are blocked by inhibition of the the calcium-calcineurin-NFAT signaling pathway. in response to increases in intracellular calcium, Calcineurin (CN) dephosphorylates NFAT transcription factors, thus, they become transcriptionally active. Some metalloproteinases are among VEGF/Ang-II-regulated genes, which participate in vascular remodeling, modifying ECM. Adamts-1 (A Disintegrin and Metalloproteinase with Thrombospondin motifs type I), mainly degrades proteoglycans. Mechanisms which regulate Adamts-1 gene expression during vascular remodeling have not been fully elucidated. Our findings indicate that VEGF and Ang-II increase Adamts-1 expression through differential signal transduction pathways, which specifically switch on the activity of NFAT or C/EBPβ transcription factors respectively, in both endothelial (EC) and smooth muscle cells (VSMCs).
18th International Vascular Biology Meeting. Kyoto, 14-17 Apr. 2014
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