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dc.contributor.advisor Schäfer, Katrin Prof. Dr.
dc.contributor.author Schremmer, Carmen
dc.date.accessioned 2013-10-02T11:52:53Z
dc.date.available 2013-11-14T23:50:04Z
dc.date.issued 2013-10-02
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-0001-BBBE-C
dc.language.iso deu de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc 610 de
dc.title Bedeutung von Urokinase-Plasminogen-Aktivator für das Wachstum und die Stabilität arteriosklerotischer Gefäßläsionen im Apolipoprotein-E-Knockout-Mausmodell de
dc.type doctoralThesis de
dc.title.translated Lack of urokinase plasminogen activator promotes progression and instability of atherosclerotic lesions on apolipoprotein E-knockout mice de
dc.contributor.referee Schäfer, Katrin Prof. Dr.
dc.date.examination 2013-11-07
dc.description.abstracteng Urokinase plasminogen activator (uPA) is strongly expressed in atherosclerotic lesions, but the overall effect of the protease on plaque composition and growth remains controversial. In the present study, apolipoprotein E-deficient (apoE-/-) mice were intercrossed with mice which were lacking the uPA gene (doubleknockout; DKO). In ferric chloride-induced carotid artery lesions in chow-fed mice, uPA deficiency increased neointimal size (P=0.015) and luminal stenosis (P=0.014), while reducing media thickness (P=0.002). A lack of uPA also increased the size of and the luminal obstruction from atherosclerotic plaques at the coronary and brachiocephalic arteries of apoE-/- mice. Plaques were characterised by a higher fibrinogen/fibrin content and a decrease in cellularity and collagen content. When apoE-/- and DKO mice were analysed as a single group, a significant correlation was found between the α-actin (smooth muscle cell) and collagen content of atherosclerotic lesions (r=0.554; P<0.05), and a negative correlation existed between the α-actin and fibrin/fibrinogen immunopositive area (r = –0.791;P<0.001). Further analysis of brachiocephalic atherosclerosis, a predilection site for plaque rupture in the apoE-/- mouse, revealed signs of plaque vulnerability, including a reduced cap-to-intima ratio (0.21±0.04 vs. 0.37±0.05; P=0.03) and more frequent detection of intraplaque haemorrhage (56% vs. 13%; P<0.01) and buried fibrous caps (1.8±0.5 vs. 0.5±0.2; P=0.02) in DKO compared to apoE-/- mice.These results indicate that, at least at (patho)physiologic concentrations, uPA is essential for maintaining the cellularity and collagen content and, possibly, the stability of lesions, both by preventing excessive intramural fibrin accumulation and by facilitating cell migration and invasion. de
dc.contributor.coReferee Patschan, Daniel PD Dr.
dc.subject.eng Atherosclerosis de
dc.subject.eng Restenosis de
dc.subject.eng Arterial thrombosis de
dc.subject.eng mouse model de
dc.subject.eng Urokinase de
dc.subject.eng Urokinase receptor de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BBBE-C-9
dc.affiliation.institute Medizinische Fakultät de
dc.subject.gokfull Medizin (PPN619874732) de
dc.description.embargoed 2013-11-14
dc.identifier.ppn 769106544

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