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Bedeutung von Urokinase-Plasminogen-Aktivator für das Wachstum und die Stabilität arteriosklerotischer Gefäßläsionen im Apolipoprotein-E-Knockout-Mausmodell

dc.contributor.advisorSchäfer, Katrin Prof. Dr.
dc.contributor.authorSchremmer, Carmen
dc.date.accessioned2013-10-02T11:52:53Z
dc.date.available2013-11-14T23:50:04Z
dc.date.issued2013-10-02
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0001-BBBE-C
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-4077
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc610de
dc.titleBedeutung von Urokinase-Plasminogen-Aktivator für das Wachstum und die Stabilität arteriosklerotischer Gefäßläsionen im Apolipoprotein-E-Knockout-Mausmodellde
dc.typedoctoralThesisde
dc.title.translatedLack of urokinase plasminogen activator promotes progression and instability of atherosclerotic lesions on apolipoprotein E-knockout micede
dc.contributor.refereeSchäfer, Katrin Prof. Dr.
dc.date.examination2013-11-07
dc.description.abstractengUrokinase 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.coRefereePatschan, Daniel PD Dr.
dc.subject.engAtherosclerosisde
dc.subject.engRestenosisde
dc.subject.engArterial thrombosisde
dc.subject.engmouse modelde
dc.subject.engUrokinasede
dc.subject.engUrokinase receptorde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0001-BBBE-C-9
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullMedizin (PPN619874732)de
dc.description.embargoed2013-11-14
dc.identifier.ppn769106544


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