Das Aortenaneurysma ist eine häufige Erkrankung, welche mit der gravierenden Kompli-kation einer Aortenruptur einhergehen kann. In den letzten 20 Jahren konnten beachtliche kurative Fortschritte erzielt werden, welche u.a. auf die Ergänzung der rein operativen Therapie um endovaskuläre und Hybridverfahren zurückzuführen sind. Dennoch ist die Aneurysmaruptur mit einer außerordentlich hohen Mortalität assoziiert. Die Genese des Aortenaneurysmas ist multifaktoriell bedingt, sodass das Wachstumsverhalten der Aorta als Surrogat des realen Rupturrisikos schwer vorherzusagen ist. Im klinischen Alltag findet überwiegend der maximale Diameter als Größen- und Verlaufsparameter Anwendung, obwohl dadurch den heterogenen Veränderungen der Aorta möglicherweise nicht ausrei-chend Rechnung getragen wird. Ziel der Studie war es, anhand einer CT-gestützten Verlaufsquantifizierung von Aorten-veränderungen Prädiktoren für das Wachstum der Aorta abzuleiten und Wachstumsraten auf Basis unterschiedlicher morphologischer Ausgangsgrößen zu vergleichen. Zwischen den definierten Aortensegmenten konnten signifikante Unterschiede der erho-benen morphologischen Parameter wie beispielsweise der Größe, der Verteilung von Ge-fäßwand und –lumen, der Verkalkung und der Krümmung aufgezeigt werden. Diese Heterogenität ließ sich auch beim Vergleich von thorakalen/abdominalen, aneurysmati-schen/nicht aneurysmatischen und wachsenden/nicht wachsenden Segmenten bestätigen. So waren beispielweise wachsende Aortensegmente initial größer als nicht wachsende (Volumen 82 cm³ vs. 53 cm³, p < 0,00; Diameter 36 mm vs. 30 mm, p< 0,00), unterschie-den sich hingegen aber nicht hinsichtlich der Wandverkalkung (Calcium-Score 894 vs. 842, p = 0,77). Im Verlauf wiesen die wachsenden Segmente unter anderem eine stärkere Zunahme der maximalen Wandstärke (+15 % vs. +4 %, p > 0,00) und eine stärkere Elongationstendenz (Segmentlänge +3,6 % vs. -0,5 %, p < 0,00) auf. Insgesamt konnte gezeigt werden, dass im Verlauf eine Wachstumsdynamik beinahe aller erhobenen Größen bestand. Ein durchschnittliches Wachstum des Aortensegmentvolumens um 5,7 % pro Jahr gezeigt konnte werden. Unter den potentiellen Einflussfaktorenkonnten konnten als relevante Prädiktoren die ma-ximale Wandstärke, die Diameter-Längen-Ratio, die Exzentrizität der Außenzirkumferenz sowie die Risikofaktoren Rauchen und die Einnahme von Kortikoiden identifiziert wer-den. Der Vergleich morphologisch unterschiedlich basierter Wachstumsraten zeigte eine erhebliche Diskrepanz insbesondere zwischen dem Routineparameter maximaler Diameter und dem sensitiveren Volumen. Schlussfolgerung: CT-morphologisch bestimmbare Parameter wie die Wandstärke, das Proportionsmaß Diameter-Längen-Ratio und die Exzentrizität des Gefäßquerschnittes sind Prädiktoren überdurchschnittlichen Aortenwachstums. Die umfassenden routinemäßige Evaluation der Aorta mit Erhebung mehrerer morphologischer Parameter – insbesondere des Volumens – ist notwendig, um das heterogene und multifaktoriell bedingte Wachstum der Aorta suffizient zu erfassen. / Purpose This study aims to identify clinical and CT-morphologic predictors of growth of the native aorta and aortic aneurysms. Material and methods Seventy-three patients (66 ±8.0 years) who underwent two subsequent computed tomography angiographies of the thoracic/thoracoabdominal/abdominal aorta for clinical reasons from 2002 - 2008 were retrospectively included. The mean interval between the CT scans was 1.8 ±0.8 years. The aortic anatomy was divided into 9 segments from sinotubular junction to iliac bifurcation. CT scans were obtained with 16- and 64-slice scanners, all series were analyzed on a commercially available workstation. Beside the collection of information about the past medical history, several morphologic parameters were measured for each segment such as aortic volume, maximum diameter, cross sectional area, surface area, calcification, tortuosity, wall thickness or cross sectional eccentricity. Annual growth rates were calculated for each parameter. Aortic total volume was considered as the standard of reference. Therefore, aortic growth was defined as a growth rate of total volume > 5 %. Multiple regression analysis was conducted to reveal predictors of aortic growth. Results For all segments, average volumes were 65.0 ± 59.0/44.7 ± 39.6/20.3 ± 27.9 cm³ (total/lumen/wall). The annual aortic growth rate of total volume was 5.7 % for all segments. All parameters that represent the initial size of the aortic segments (total and lumen volume, maximum diameter, cross sectional area, surface area) were approved as predictors of aortic growth. Further predictors were wall volume, maximum and minimum wall thickness, diameter length ratio, segmental length and tortuosity index. Among the clinical parameters, smoking, corticosteroid medication and peripheral artery disease were confirmed as aortic growth predictors. Conclusions In clinical routine, most therapeutic decisions a made based on the diameter measurement alone, which might be inappropriate. A comprehensive evaluation of aortic morphology is warranted in the presence of increased aortic size, wall thickness, cross sectional eccentricity, smoking and corticosteroid therapy.

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.

Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a mouse model of adipocyte AT1aR deficiency using the Cre/LoxP system. Adipocyte-AT1aR deficiency confers no protection from the development of obesity or obesity- associated parameters. However, low fat fed adipocyte-AT1aR deficient mice exhibit remarkable adipocyte hypertrophy and reductions in adipocyte differentiation. These results demonstrate that AngII is a stimulus for adipocyte differentiation and adipocyte hypertrophy alone is insufficient to initiate obesity- associated disorders. In hypercholesterolemic mice, adipocyte AT1aR deficiency conferred no protection from diet or AngII-induced vascular diseases. Overall these studies suggest the primary role of adipocyte AT1aRs is to promote adipocyte differentiation and the development of small adipocytes.

A previous thoracic aortic aneurysm time course study from our laboratory determined that ascending aortic dilation was significantly increased by day 5, and reached a plateau by day 28 of angiotensin II (AngII) infusion. We also found that mice had hemorrhage localized to the ascending aortas by day 5 of AngII infusion. The purpose of these studies was to provide mechanistic insight into the development of AngII-induced ascending aortic hemorrhage. Male C57BL/6 mice fed normal diet were subcutaneously infused with either AngII (1000 ng/kg/min) or saline for 5 days. To examine cellular heterogeneity, hemorrhaged ascending aortas were collected and sectioned serially for histological staining and immunostaining. I was unable to identify an entry point for blood into the media of the aortic root and ascending aorta. However, I found incomplete intimo-medial dissection near the hemorrhaged regions that may potentially be contiguous with the blood. To investigate infiltration of immune cells during AngII infusion, immunohistochemistry of hemorrhaged ascending aortas was performed. The numbers of macrophages and neutrophils in AngII-infused aortas were increased in both medial and adventitial areas when compared with saline-infused aortas. Therefore, infiltration of immune cells at the point of dissection is associated with aortic hemorrhage during AngII infusion.

The occurrence of clinically diagnosed and/or ruptured abdominal aortic aneurysms (AAAs) in the families of 220 patients with AAAs, treated at the Surgical Clinic, University Hospital of Umeå in the northern part of Sweden during the years 1965-82, was studied. A questionnaire concerning the blood relatives was answered by 87/89 patients. 16/87 patients (18%) had blood relatives with AAAs. In 14 families one blood relative was affected, and in 2 families two blood relatives were affected. First degree relatives were affected in 9/87 cases (10%), and second degree relatives in 7/87 cases (8%). 9/468 (1.9%) of the patients' brothers and sisters but only five of all their cousins had AAAs, and 7/204 (3.4%) of the dead brothers and sisters had died of ruptured AAAs. Concerning the patients who were not included in the letter survey at least 14/133had blood relatives with AAAs. However, the great majority of these patients were dead when the study was performed and could not be asked aboutthe occurrence of AAAs in their families. The patients with AAAs had significantly higher serum concentrations of triglyceride and (YLDL + LDL)-cholesterol and a significantly lower serum concentration of HDL-cholesterol than randomly selected healthy controls of the same sex and age as the patients. We also compared the distributions of genetic markers (HLA antigens, the blood group systems ABO, Rh, MNSs, P, Kell, Lewis and Duffy and the serum protein group systems haptoglobin, transferrin, group-specific component, complement C3, properdin factor and alpha-1-antitrypsin) in patients with AAAs with the distributions in controls and in some cases with the expected distributions according to the Hardy-Weinberg law. A significantly decreased frequency of Rh-negative individuals, and significantly increased frequencies of Kell-positi ve individuals, of MN heterozygotes and of heterozygotes concerning haptoglobin type was found. Furthermore, the aneurysm walls of patients with and without AAAs in the family were compared concerning the morphology, but no differences were found. We also studied the occurrence of collagen types I and III in the aneurysm walls, and the occurrence of vimentin and desmin in the smooth muscle cells of the aneurysm walls, but all these components were present in the aneurysm walls of both the patients with and those without AAAs in the family. To summarize the results, there seems to be an increased frequency of AAAs, and especially of ruptured AAAs, among the brothers and sisters of patients with AAAs. Elevated serum concentrations of triglyceride and (VLDL + LDL)- cholesterol and a lowered serum concentration of HDL-cholesterol seems to be common in patients with AAAs. There seems to be a hereditary predisposition to the development of AAAs, because we found associations with four different genetic markers (Rh, MN, Kell, haptoglobin group). However, there is probably no specific "familial" type of AAAs, because we found no differences between the patients with and those without AAAs in the family.Key words: / <p>S. 1-42: sammanfattning, s. 43-103: 5 uppsatser</p> / digitalisering@umu

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.

Turbulent flow downstream of a bileaflet mechanical heart valve is investigated using digital particle image velocimetry. Evolution of flow structures during the systole and diastole phases of a typical cardiac cycle is characterized by obtaining global flow velocity measurements in multiple cross-sections of the flow field. Instantaneous and time-averaged patterns of flow velocity, vorticity, and streamline topology are used to illustrate the interaction between the unsteady vortices that results in elevation of shear stress levels. This image-based approach can potentially lead to development of methods of control of platelet activation and provides insight into the underlying flow physics.

No description available.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [197]-225).

Thesis (M. S.)--Chemical and Biomolecular Engineering, Georgia Institute of Technology, 2005. / Dr. Athanassios Sambanis, Committee Member ; Dr. Timothy M. Wick, Committee Member ; Dr. Ajit P.Yoganathan, Committee Chair. Includes bibliographical references.