caa a22 4500 463185439 CHVBK 20180406164851.0 cr unu---uuuuu 170326e20070101xx s 000 0 eng 10.1007/s00726-006-0376-0 doi (NATIONALLICENCE)springer-10.1007/s00726-006-0376-0 Could activated tissue remodeling be considered as early marker for progressive valve degeneration? Comparative analysis of checkpoint and ECM remodeling gene expression in native degenerating aortic valves and after bioprosthetic replacement [Elektronische Daten] [K. Yeghiazaryan, D. Skowasch, G. Bauriedel, H. Schild, O. Golubnitschaja] Summary.: Objectives. Aortic stenosis is the leading cause of heart valve disease in elderly. Little is known about molecular mechanisms leading to altered left ventricular geometry generally and, particularly, to remodeling of degenerating aortic valve. Alterations in native degenerating aortic valves and valvular tissue after replacement might result from a stage specific tissue remodeling protein core induced by stress responsible factors. Here we were looking for a possible stage specificity of tissue remodeling and stress responsive checkpoint gene activation in native degenerating human aortic valves and bioprosthetic valvular tissue after replacement. Materials and methods. Specimens of native degenerating aortic valves as well as bioprosthetic valves after replacement were tested for their morphological properties. Native degenerating valves were selected for two groups: non-calcified (7 samples) and calcified (5 samples) one; the third group (5 samples) was consisting of bioprosthetic valve samples after replacement. Individual mRNA-pools were isolated from each tissue sample, and semi-quantitative RT-PCR was performed. Target transcripts of p21waf1/cip1, MT1-MMP, MMP-2, MMP-9 and TIMP-1 were measured. The specificity was controlled by restriction analysis of PCR products. Results and conclusions. According to the abundant expression of p21waf1/cip1, a highly activated stress response was found in non-calcified native degenerating aortic valves, whereas no stress response was monitored in valvular tissue after replacement. Whereas MT1-MMP expression was almost equally induced in all three groups investigated, MMP-9 was higher expressed in non-calcified versus calcified native valves, and was not expressed after replacement. An induced expression of MMP-2 was detected in non-calcified native degenerating aortic valves only. An abundant expression of tissue inhibitor of metalloproteinases TIMP-1 was observed in all three groups tested. Apparently, the ECM degradation potential is specifically enhanced in non-calcified native degenerating aortic valves e.g. at the early degeneration stages. In contrast, the replaced valves were found to be actively resorbing tissue with no detectable stress response, where both MT1-MMP and TIMP-1 might play the key role in geometry remodeling. Springer-Verlag, 2006 Keywords: Degenerating aortic valves - Bioprosthetic valvular replacement - Stress responsive checkpoints - Extracellular matrix remodeling - Metalloproteinases - Diagnostic molecular marker nationallicence Yeghiazaryan K. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut Skowasch D. Department of Cardiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut Bauriedel G. Department of Cardiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut Schild H. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut Golubnitschaja O. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut Amino Acids Springer-Verlag 32/1(2007-01-01), 109-114 0939-4451 32:1<109 2007 32 726 https://doi.org/10.1007/s00726-006-0376-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-006-0376-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yeghiazaryan K. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Skowasch D. Department of Cardiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Bauriedel G. Department of Cardiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Schild H. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Golubnitschaja O. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 32/1(2007-01-01), 109-114 0939-4451 32:1<109 2007 32 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer