During endovascular aneurysm repair (EVAR), if the stent-graft device is too long for a given patient the redundant (extra) length adopts a convex configuration in the aneurysm. Based on clinical experience, we hypothesize that redundant stent-graft configurations increase the downward force acting on the device, thereby increasing the risk of device dislodgement and failure. This work numerically studies both steady-state and physiologic pulsatile blood flow in redundant stent-graft configurations. Computational fluid dynamics simulations predicted a peak downward displacement force for the zero-, moderate- and severe-redundancy configurations of 7.36, 7.44 and 7.81 N, respectively for steady-state flow; and 7.35, 7.41 and 7.85 N, respectively for physiologic pulsatile flow. These results suggest that redundant stent-graft configurations in EVAR do increase the downward force acting on the device, but the clinical consequence depends significantly on device-specific resistance to dislodgement.

During endovascular aneurysm repair (EVAR), if the stent-graft device is too long for a given patient the redundant (extra) length adopts a convex configuration in the aneurysm. Based on clinical experience, we hypothesize that redundant stent-graft configurations increase the downward force acting on the device, thereby increasing the risk of device dislodgement and failure. This work numerically studies both steady-state and physiologic pulsatile blood flow in redundant stent-graft configurations. Computational fluid dynamics simulations predicted a peak downward displacement force for the zero-, moderate- and severe-redundancy configurations of 7.36, 7.44 and 7.81 N, respectively for steady-state flow; and 7.35, 7.41 and 7.85 N, respectively for physiologic pulsatile flow. These results suggest that redundant stent-graft configurations in EVAR do increase the downward force acting on the device, but the clinical consequence depends significantly on device-specific resistance to dislodgement.

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Στην παρούσα Διπλωματική Εργασία μελετάται η ανάπτυξη ενός μοντέλου προσομοίωσης αλληλεπίδρασης ρευστού-στερεού για τον προσδιορισμό ρευστοδυναμικών παραμέτρων (Wall Shear Stress, Von Mises Stress κ.α.) μέσω των οποίων θα μπορεί μελλοντικά να προβλεφθεί η ρήξη ή όχι ενός ενδοκρανιακού ανευρύσματος. Αρχικά γίνεται μια σύντομη παρουσίαση του ιατρικού προβήματος ώστε να γίνει κατανοητή η σπουδαιότητα της ανάπτυξης του υπολογιστικού μοντέλου με σκοπό τον υπολογισμό παραμέτρων οι οποίες μπορούν να φανούν χρήσιμες. Κατά τη διάρκεια ανάπτυξης του μοντέλου αξιοποιήθηκαν πραγματικά δεδομένα απεικονιστικών διατάξεων ασθενών του Αττικού Πανεπιστημιακού Γενικού Νοσο- κομείου. Εν συνεχεία, η επεξεργασία των εικόνων αυτών διεξήχθει στο λογισμικό ανοιχτού κώδικα VMTK (Vascular Modeling Toolkit) από όπου προήλθε και η τρισδιάστα- τη ανακατασκευη τους. Στο επόμενο στάδιο, οι γεωμετρίες που προέκυψαν από την επεξεργασία εικόνας εισήχθησαν στο λογισμικό εμπορικού κώδικα ANSYS όπου και αναπτύχθηκε το υπολογιστικό μοντέλο το οποίο περιείχε και την αλληλεπίδραση ρευστού και στερεού (FSI). Αξίζει να αναφερθεί το γεγονός ότι το μοντέλο που αναπτύχθηκε περιείχε κινούμενα στοιχεία πλέγματος (Moving Mesh), τα οποία συμβάλλουν στον ακριβέστερο υπολογισμό και αποτύπωση παραμέτρων που υπολογίστηκαν στη συνέχεια. Τέλος αναφέρονται κάποιοι μελλοντικοί στόχοι και προοπτικές μέσω των αποτελεσ- μάτων που προέκυψαν από την ανάλυση του μοντέλου. / In the present M.Sc thesis we are studying the development of a numerical model that simulates fluid-solid interaction for determining fluid dynamics parameters (Wall Shear Stress, Von Mises Stress etc) through which through which could be predicted the rupture or not of an intracranial aneurysm. First, a brief presentation of the medical problem is being made, to understand the importance of developing the computational model in order to calculate parameters which can be useful. During the development of the model, real imaging data from CT scans taken from patients of Attikon General University Hospital were exploited. Thereafter, the processing of these images was performed in the open-source software VMTK (Vascular Modeling Toolkit) from where came the three-dimensional reconstruction. In the next step, the geometries obtained from the image processing have been introduced in the commercial software ANSYS where the computational model that contains the interaction of fluid and solid has been developed (FSI). It is worth mentioning that the model developed, contained moving mesh elements, which contribute to more accurate calculation and mapping of parameters which were calculated after. Finally, some future objectives and prospects are being referred, through the results obtained from the analysis of the model.

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The purpose of this study was to determine whether androgen promotes AT1aR expression on smooth muscle to confer high prevalence of AngII-induced AAAs in hyperlipidemic mice. In addition, we also investigate the role of androgen in the progression of established AngII-induced AAAs. First, we sought to examine the role of endogenous androgen in the growth of established AngII-induced AAAs. By castrating male mice, we demonstrated that removal of endogenous androgen significantly decreased the progressive lumen dilation of established AngII-induced AAAs in male ApoE-/- mice, but had no effect on external AAA diameters. These results suggest that androgen contributes to the progression of established AAAs through distinct mechanisms that differentially influence aortic lumen and wall diameters. We also investigate whether androgen regulates aortic AT1aR expression to promote AngII-induced AAA formation. Our data demonstrated that in male and female mice, both endogenous and exogenous androgen stimulate AT1aR level particularly in abdominal aortas. This androgen-dependent enhanced expression of abdominal aortic AT1aR was correlated with increased AngIIinduced AAA formation in male and female mice. Smooth muscle AT1aR deficiency significantly reduced luminal and external diameters of abdominal aortas as well as the incidence of AngII-induced AAAs in adult female mice administered exogenous androgen. Collectively, these results indicate that in adult mice androgen stimulate smooth muscle AT1aR expression to promote AngII-induced AAA formation. To determine the role of androgen during development on AT1aR expression on SMC and AngII-induced vascular pathologies, we exposed neonatal female mice to one single dose of testosterone. Our data demonstrated that neonatal testosterone administration dramatically increased AngII-induced AAA, atherosclerosis and ascending aortic aneurysms in adult female mice. In addition, smooth muscle AT1aR deficiency reduced effects of neonatal testosterone to promote AAAs, but had no effect on the other two AngII-induced vascular pathologies. In summary, our findings demonstrated that androgen, both in adult life and during development, stimulate smooth muscle AT1aR expression and promote AngII-induced AAA in female hyperlipidemic mice.

Previous studies demonstrated that coplanar PCBs promote inflammation by release of pro-inflammatory cytokines like TNF, MCP-1, and VCAM-1 from endothelial cells as well as adipocytes. Also these PCBs at small doses may contribute to the development of obesity by inducing adipocyte differentiation. Obesity is a known risk factor that promotes cardiovascular disorders like atherosclerosis and AAAs. Evidence shows Ang II, a component of the RAS, leads to the formation of atherosclerosis and AAAs in both normal as well as hyperlipidemic mice. Earlier studies in our laboratory have also shown that coplanar PCB-77 promotes atherosclerotic lesion formation in ApoE-/- mice. The purpose of this study was to define the effects of PCB77 on Ang II induced vascular diseases like atherosclerosis and AAAs. Two different hyperlipidemic mouse models, which require different diets to get atherosclerosis, the ApoE deficient mice (ApoE-/-) requiring the normal mouse diet (Chow diet) and the Low Density Lipoprotein Receptor deficient mice (LDLr-/-) requiring the Western diet, were used for this study as both are susceptible to Ang II induced vascular disorders. The timing of PCB administration was also studied in LDLr-/- mice to see the profound effects of PCB77 on atherosclerosis and AAAs.

This project concerns an exploration of the presence and interactions of long non-coding RNA transcripts in an experimental atherosclerosis mouse model with relevance for human abdominal aortic aneurysm development. 187 long noncoding RNAs, two of them entirely novel, were found to be differentially expressed between angiotensin II treated (developing abdominal aortic aneurysms) and non-treated apolipoprotein E deficient mice (not developing aneurysms) harvested after the same period of time. These transcripts were also studied with regards to co-expression network connections. Eleven previously annotated and two novel long non-coding RNAs were present in two significantly disease correlated co-expression groups that were further profiled with respect to network properties, Gene Ontology terms and MetaCore© connections.

Background: Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms. Methods: Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genotyped for the following polymorphisms: methionine synthase (MTR) c.2756A→G, methylenetetrahydrofolate reductase (MTHFR) c.677C→T, MTHFR c.1298A→C, cystathionine β-synthase (CBS) c.844_855ins68, CBS c.833T→C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Ω-1 (GSTO1) c.428C→A, reduced folate carrier 1 (RFC1) c.80G→A and transcobalamin 2 (Tc2) c.776C→G. Results: The G-allele of the missense polymorphism Tc2 c.777C→G was found to be underrepresented in patients, suggesting that this variant may protect from the formation of cerebral aneurysms [odds ratio per two risk alleles (OR) 0.48; 95% confidence interval (CI) 0.30–0.77; p = 0.002]. We obtained borderline results for the G-allele of RFC1 c.80G→A (OR 1.64; 95% CI 1.01–2.65; p = 0.051) and the insertion allele of DHFR c.594 + 59del19bp (OR 1.61; 95% CI 1.00–2.60; p = 0.059), which were found to be overrepresented in patients. Conclusion: Polymorphisms of homocysteine metabolism are possible risk factors for the formation of intracranial aneurysms. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.