Die Charakterisierung der differentiellen Genexpression invasiver und nicht-invasiver humaner glatter Gefäßmuskelzellen
The ability of smooth muscle cells to proliferate and migrate plays a decisive role in the pathogenesis of cardiovascular disorders, like arteriosclerosis and coronary heart disease as well as in restenosis after percutaneous transluminal angioplasty and stent implantation.The objective of this dissertation was to identify genes which are responsible for proliferation and migration of smooth muscle cells (SMC). Under cell culture conditions 2 phenotypes of smooth muscle cells were induced with diverging potentials of migration and invasion. This potential was tested in a modified Boyden Chamber. The phenotypes act as a model of non-invasive smooth muscle cells in healthy arterial wall respectively smooth muscle cells capable of proliferation and migration after PTCA. Using a cDNA array system 558 cardiovascular-associated genes could be compared. Further, gene expression was exactly quantified by real-time RT-PCR. Protein expression was analyzed by ELISA and Western blotting. In total, 47 genes were differentially expressed more than 1.5 times. A significant role of genes associated with the extracellular matrix (ECM), cell-adhesion, cell motility and matrix-organizing proteins was shown using functional classification and cluster analysis. Matrix-organizing proteins and ECM proteins were upregulated in invasive smooth muscle cells, proteins of the metabolism and cell adhesion in non-invasive SMC. Besides genes known to be differentially regulated during SMC migration and invasion like matrix-metalloproteinases (MMP) and their inhibitors (TIMP) new genes not previously mentioned in the context of restenosis were detected like angio-associated protein (AAMP), atrial brain natriuretic factor (BNP-Rezeptor), alpha E-catenin and TFPI II. In conclusion, several relevant potential candidate genes for the quiescent and the invasive SMC phenotype were identified and genes already known to be differentially regulated by previous analysis were confirmed.
info:eu-repo/classification/ddc/610, Medizin, glatte Gefäßmuskelzellen, Restenose, Migration, Invasion
Networked Digital Library of Theses and Dissertations
Publikationsserver der RWTH Aachen University