Bakgrund: Bröstcancer är den vanligaste cancerformen hos kvinnor i Sverige. Riskfaktorerna är flera och därför har Socialstyrelsen bestämt att hälso- och sjukvården ska erbjuda mammografiscreening för att upptäcka sjukdomen i ett tidigt stadium. Bukaortaaneurysm är en lokal vidgning av kroppspulsådern som främst drabbar män. Sjukdomen är ofta asymtomatisk och kan vara livshotande. Socialstyrelsen har därför bestämt att en engångsundersökning ska erbjudas alla män i 65-års ålder. Syfte: Syftet med examensarbetet var att studera anledningar till utebliven screeningundersökning och om anledningarna skiljer sig åt för mammografi- och bukaortascreening. Metod: Detta examensarbete är en litteraturöversikt som behandlar 15 vetenskapliga artiklar relevanta till arbetets syfte. Resultat: Faktorer som påverkade deltagandet var: ålder, invandring, nära relation till sjukdomen, avstånd, svårigheter att ta sig till klinik/opassande öppettider, utbildning, social status, fysisk och psykisk ohälsa, okunskap/bristande information, rädslor/förnekelse, civilstånd/familj och mottagen påminnelse. Diskussion: Samtliga punkter för icke deltagande stämde inte alltid överens för de båda screeningprogrammen. Efter granskning av inbjudan till screeningprogrammen sågs skillnader i informationen som skulle kunna ha betydelse för de faktorer som studerats i artiklarna. Slutsats: Icke deltagande kan bero på flera faktorer som påverkas av varandra och en liten skillnad mellan män och kvinnor sågs. Inbjudan kan påverka deltagandet i vissa fall. / Background: Breast cancer is the most common form of cancer in women in Sweden and there are several risk factors. Abdominal aortic aneurysm is an expansion of the vessel and men are most likely to suffer. The disease is asymptomatic and life-threatening. The National Board of Health and Welfare has decided to offer mammography screening and aneurysm screening to detect the diseases in an early stage. Aim: The aim with this review was to study reasons for non-participation in screening and if reasons differ from the both screening programme. Method: This bachelor thesis was designed as a review based on 15 articles. Results: Factors that affect the attendance was: age, immigration, close relations to the disease, distance, disable to get to the clinic/unfitting opening hours, education, social status, physical/mental health, unknowledge/less information, fear/denial, civil status/family and reminder letter. Discussion: Factors for non-attendance was not the same for both screening programmes. Inspection of the invitation letter from Jönköping county showed some defects that could affect the factors that has been found in the articles. Conclusion: Non-attendance can depend on several factors that influence each other and small differences was seen between men and women. The invitation letter could affect the participation in some cases.

A Síndrome de Marfan (MFS) é uma doença autossômica dominante do tecido conjuntivo, que acomete principalmente os sistemas esquelético, ocular e cardiovascular. O fenótipo cardiovascular, em especial o aneurisma de aorta, é responsável pela maior parte da morbi-mortalidade. MFS é resultante da mutação da fibrilina-1, uma glicoproteína que além de ser um dos principais componentes estruturais da matriz extracelular, tem como função a regulação da atividade do TGF-Beta, por meio de seu sequestro mecânico na matriz extracelular. No entanto, os mecanismos pelos quais a mutação da fibrilina-1 determina aneurismas de aorta torácica com elevada variabilidade fenotípica são ainda pouco elucidados. Um alvo central na fisiopatologia do aneurisma são células musculares lisas vasculares (VSMC), que constituem a maior porção da camada média da aorta. Por meio do controle do tônus contrátil da aorta, da estrutura do citoesqueleto e da interação com a matriz extracelular controlam a estrutura da aorta e a resposta a estímulos patológicos. Mutações que geram perda de função no aparato contrátil de VSMCs prejudicam força contrátil e respostas mecanoadaptativas. No entanto, o papel da VSMC na MFS foi pouco estudado. Neste estudo, investigamos se alterações do fenótipo de VSMCs correlacionam-se a prejuízos na geração de força e alterações em respostas biomecânicas em VSMC cultivadas a partir de aortas obtidas de camundongos com ou sem a mutação mgDeltalpn para MFS na fase inicial (3 meses) e tardia (6 meses). Aos 3 meses de evolução, detectamos importantes alterações fenotípicas nas MFS-VSMC, com maior proliferação celular e redução de alguns marcadores de diferenciação (calponina-1), porém aumento de outros (alfa-actina e SM22). Ao mesmo tempo, ocorreu mudança morfológica, com aumento da área da célula e perda do formato fusiforme. Tais alterações foram consistentes com transição para fenótipo mesenquimal, que foi confirmada pela expressão de vários marcadores. Marcadores de estresse do retículo endoplasmático (RE) aumentaram em MFS-VSMC vs. WT (wild-type) -VSMC condição basal, sem aumento pós estiramento mecânico. Correção da matriz de fibrilina-1 defeituosa em MFS-VSMC promoveu reversão de alguns aspectos do fenótipo, mas não do estresse do RE. MFS-VSMC mostra perfil protêomico divergente de WT-VSMC, em particular menor expressão de proteínas regulatórias do citoesqueleto. Importante, MFSVSMC têm reduzida capacidade de gerar força de tração quando semeadas em substrato com rigidez fisiológica e geram momento contrátil in vitro, no entanto, sem perda na capacidade de adesão. Importante, MFS-VSMC têm forte atenuação da resposta de tração a aumentos da rigidez do substrato. Em paralelo, MFS-VSMC exibem menor densidade em fibras de estresse de actina em relação às WT-VSMC. A maioria destas alterações não foram observadas aos 6 meses de evolução da doença. Os dados indicam que na fase precoce da doença, MSF-VSMC exibem mudanças fenotípicas que vão além de uma simples modulação fenotípica, com aspectos de transição mesenquimal e reduzida capacidade de geração de força tensional associada não à adesão celular, porém à menor capacidade de geração de fibras de estresse de actina. Estes mecanismos, descritos pela primeira vez, contribuir para elucidar a fisiopatologia da MFS, com alguns aspectos comuns, porém outros distintos de outras modalidades de aneurisma de aorta / Marfan Syndrome (MFS) is an autosomal dominant connective tissue disease affecting to variable extents the musculoskeletal, ocular and cardiovascular systems. Cardiovascular phenotype and in particular thoracic aorta aneurysm/dissection (TAAD), is responsible for the bulk of disease morbimortality. MFS is due to mutations in fibrillin-1, one of the main structural proteins of the extracellular matrix (ECM), which in addition regulates TGF-Beta activity by means of its physical retention in the ECM. However, mechanisms by which fibrillin-1 mutation determines TAAD with elevated phenotypic variability are yet poorly understood. Vascular smooth muscle cells (VSMC), the main component of aortic medial layer, are central targets of aneurysm pathophysiology in general. By exerting regulation of contractile tone, cytoskeletal structure and ECM interaction, VSMC control aortic structure and response to pathologic stimuli. Mutations that promote loss of VSMC contractile apparatus impair contractile function and mechanoadaptative responses and associate with distinct types of TAAD. However, the role of VSMC mechanobiology in MFS pathophysiology is poorly known. In this study, we investigated whether VSMC loss of force-generating capacity occurs in MFS and whether it associates with specific changes in cell phenotype. Biomechanical VSMC responses were assessed in cells cultured from aortas collected from mice with the mgDeltalpn MFS mutation at early (3-monthold mice, the main focus of our study) and advanced (6-month-old mice) stages of disease evolution. At 3 months of disease evolution, we detected important phenotypic alterations in MFS-VSMC, with enhanced expression of markers for cellular proliferation and lower expression of some differentiation markers (calponin-1), but, increase in others (SM alfaactin and SM22). In parallel, there were important morphologic changes, with increased VSMC area and loss of its fusiform shape. Such alterations are consistent with a transition towards a mesenchymal-like phenotype, which was confirmed through the expression of several markers. Endoplasmic reticulum (ER) stress markers increased in MFS-VSMC vs. WT (wild-type)-VSMC in basal condition, without augmentation after cyclic mechanical stretching. Replacement of defective fibrillin-1 ECM from MFS-VSMC with a normal fibroblast-derived ECM promoted reversion of some aspects of the phenotype but not of ER stress. MFS-VSMC exhibited a proteomic profile divergent from that of WT-VSMC, particularly with respect to the lower expression of cytoskeleton regulatory proteins. Importantly, MFS-VSMC displayed a lower traction force-generating capacity when seeded in ECM under physiological stiffness and generated an impaired contractile moment in this situation. In particular, MFS-VSMC depicted a strong attenuation of the traction force response to enhanced ECM stiffening. These defects did not occur as a result of lower adhesion structure and decreased adhesion capacity of MFS-VSMC. In parallel, MFS-VSMC exhibited lower density of actin stress fiber vs. WT-VSMC. With 6 months of disease evolution, several of these alterations were not detectable. Both WTVSMC and MFS-VSMC showed reduced capacity of force generation, without evidence of cell senescence. In summary, starting already in the early stages of disease evolution, MSF-VSMC display important phenotypic changes which go beyond a simple reversible phenotypic modulation, with some aspects suggesting a transition mesenchymal-like phenotype, accompanied by reduced force-generating capacity not linked to loss of cell adhesion properties but rather to impaired organization of action stress fibers. These mechanisms, described for the first time, contribute to elucidate MFS pathophysiology, depicting both some aspects in common with the pathophysiology of other types of aortic aneurysm and some aspects peculiar to MFS

Aneurisma de Aorta Abdominal (AAA) é definido como uma dilatação localizada e permanente da parede arterial, geralmente com ocorrência entre as artérias renais e as ilíacas, como conseqüência do enfraquecimento dessa parede ou devido a uma solicitação anormal sobre sua estrutura normal. Essa afecção acomete principalmente a população idosa acima de 65 anos de idade, tendo como principais fatores de risco: tabagismo, hipertensão arterial, histórico familiar e doença obstrutiva crônica pulmonar. A prevalência está aumentando nos últimos anos, havendo uma duplicação dos casos diagnosticados nos Estados Unidos (Bonamigo e Von Ristow, 1999). Hoje o AAA é a 13ª causa de morte nos Estados Unidos, em homens com mais de 65 anos e no caso de aneurisma roto, é a 3ª causa de morte súbita nos Estados Unidos. A mortalidade global do AAA roto está em torno de 80% nos países que têm verificação sistemática e compulsória da causa de óbitos. Isto ocorre devido ao fato de uma hemorragia substancial intra-abdominal geralmente ser acompanhada de atraso no transporte e diagnóstico, e da necessidade de cirurgia de emergência em pacientes idosos que, freqüentemente, tem uma significativa comorbidade renal e cardiopulmonar. Acredita-se que a formação e o crescimento do aneurisma de aorta abdominal são acompanhados do crescimento da tensão na parede da aorta e/ou de uma diminuição da capacidade do tecido de suportar tal tensão. A ruptura ocorre quando a tensão atuante na parede excede a tensão que pode ser suportada pelo tecido. O risco de ruptura aumenta com o crescimento do tamanho do aneurisma, da tensão na parede e é agravado quando associado à hipertensão arterial. No estudo foram obtidos dados morfológicos da região torácica de um paciente com a utilização de tomografia computadorizada multi-fatias. Essas imagens DICOM (Comunicação de Imagens Digitais em Medicina) foram tratadas para selecionar apenas a região de interesse, obtendo-se um modelo tridimensional da aorta infra-renal e artérias ilíacas. A partir daí, foi confeccionado um modelo físico com a utilização de prototipagem rápida. Um simulador cardiovascular controlado por computador foi desenvolvido com o intuito de replicar características fisiológicas e patológicas do sistema cardiovascular humano. Esse modelo de aneurisma foi utilizado para simulação em bancada experimental, onde é possível reproduzir alguns parâmetros como pressão, fluxo, temperatura, resistência e complacência vascular. Também foi gerado um modelo computacional onde os parâmetros obtidos na simulação in vitro foram utilizados como condição de contorno inicial para o estudo computacional. Foram adotados padrões normotenso e hipertenso, e os resultados computacionais e experimentais foram analisados e comparados. O trabalho propõe uma metodologia que possibilite a obtenção de dados anatômicos e hemodinâmicos relativos ao segmento arterial acometido pela afecção, com o objetivo de fornecer informações adicionais no diagnóstico do aneurisma de aorta. / Abdominal Aortic Aneurysm (AAA) is defined as a focal and permanent dilatation of the arterial wall, most often occurring in between the renal and iliac arteries, as consequence of arterial wall weakness or because of an abnormal solicitation of that normal structure. This disease primarily affects elderly population over 65 years of age, and the most important risk factors are smoking, hypertension, family history and chronic obstructive pulmonary disease. In the last years, the prevalence is rising up almost twice the diagnosed cases in the United States (Bonamigo and Von Ristow, 1999). Nowadays, AAA is the thirtieth cause of death in the United States, in the elderly masculine population over 65 years of age, and in case of ruptured aneurysm, it is the third cause of sudden death in the United States. The overall mortality rate is about 80% in countries with systematic and compulsory evaluation of death cause. This is due to the fact that substantial intra-abdominal hemorrhage is often accompanied by delays in transport and diagnoses, and the need for emergency surgery in elderly patients that frequently have significant renal and cardiopulmonary comorbidity. It is suggested that the formation and expansion of the AAA are accompanied by wall stress increasing and / or decreasing in the tissue capacity to withstand this stress. The rupture occurs when the wall stress exceed the stress the tissue can accept. The risk of rupture increases with aneurysm expansion, wall stress increasing and it is exacerbated when associated with arterial hypertension. In the present work, morphological data from thoracic region of the patient was acquired by using multi-slice CT (Computed Tomography). These DICOM images had been treated to select only the interest region, getting a three-dimensional infra-renal aortic and iliac model. Then, it was made a physical model by using rapid prototyping. This model was used for in vitro experimentation in a computer controlled mock system, in which it is possible to replicate physiological and pathological characteristics of human being cardiovascular system. Some parameters such as pressure, flow, temperature, vascular resistance and compliance can be reproduced by the use of a mock circulatory system. These parameters were used as initial boundary conditions in order to calibrate a computational model. It was adopted normotensive and hypertensive patterns and computational and experimental results were analyzed and compared. The paper proposes a methodology which allows the acquisition of anatomical and hemodynamic data on the vessel segment affected by the pathology, with the goal of providing additional information in the diagnosis of aortic aneurysm.

Aneurisma de Aorta Abdominal (AAA) é definido como uma dilatação localizada e permanente da parede arterial, geralmente com ocorrência entre as artérias renais e as ilíacas, como conseqüência do enfraquecimento dessa parede ou devido a uma solicitação anormal sobre sua estrutura normal. Essa afecção acomete principalmente a população idosa acima de 65 anos de idade, tendo como principais fatores de risco: tabagismo, hipertensão arterial, histórico familiar e doença obstrutiva crônica pulmonar. A prevalência está aumentando nos últimos anos, havendo uma duplicação dos casos diagnosticados nos Estados Unidos (Bonamigo e Von Ristow, 1999). Hoje o AAA é a 13ª causa de morte nos Estados Unidos, em homens com mais de 65 anos e no caso de aneurisma roto, é a 3ª causa de morte súbita nos Estados Unidos. A mortalidade global do AAA roto está em torno de 80% nos países que têm verificação sistemática e compulsória da causa de óbitos. Isto ocorre devido ao fato de uma hemorragia substancial intra-abdominal geralmente ser acompanhada de atraso no transporte e diagnóstico, e da necessidade de cirurgia de emergência em pacientes idosos que, freqüentemente, tem uma significativa comorbidade renal e cardiopulmonar. Acredita-se que a formação e o crescimento do aneurisma de aorta abdominal são acompanhados do crescimento da tensão na parede da aorta e/ou de uma diminuição da capacidade do tecido de suportar tal tensão. A ruptura ocorre quando a tensão atuante na parede excede a tensão que pode ser suportada pelo tecido. O risco de ruptura aumenta com o crescimento do tamanho do aneurisma, da tensão na parede e é agravado quando associado à hipertensão arterial. No estudo foram obtidos dados morfológicos da região torácica de um paciente com a utilização de tomografia computadorizada multi-fatias. Essas imagens DICOM (Comunicação de Imagens Digitais em Medicina) foram tratadas para selecionar apenas a região de interesse, obtendo-se um modelo tridimensional da aorta infra-renal e artérias ilíacas. A partir daí, foi confeccionado um modelo físico com a utilização de prototipagem rápida. Um simulador cardiovascular controlado por computador foi desenvolvido com o intuito de replicar características fisiológicas e patológicas do sistema cardiovascular humano. Esse modelo de aneurisma foi utilizado para simulação em bancada experimental, onde é possível reproduzir alguns parâmetros como pressão, fluxo, temperatura, resistência e complacência vascular. Também foi gerado um modelo computacional onde os parâmetros obtidos na simulação in vitro foram utilizados como condição de contorno inicial para o estudo computacional. Foram adotados padrões normotenso e hipertenso, e os resultados computacionais e experimentais foram analisados e comparados. O trabalho propõe uma metodologia que possibilite a obtenção de dados anatômicos e hemodinâmicos relativos ao segmento arterial acometido pela afecção, com o objetivo de fornecer informações adicionais no diagnóstico do aneurisma de aorta. / Abdominal Aortic Aneurysm (AAA) is defined as a focal and permanent dilatation of the arterial wall, most often occurring in between the renal and iliac arteries, as consequence of arterial wall weakness or because of an abnormal solicitation of that normal structure. This disease primarily affects elderly population over 65 years of age, and the most important risk factors are smoking, hypertension, family history and chronic obstructive pulmonary disease. In the last years, the prevalence is rising up almost twice the diagnosed cases in the United States (Bonamigo and Von Ristow, 1999). Nowadays, AAA is the thirtieth cause of death in the United States, in the elderly masculine population over 65 years of age, and in case of ruptured aneurysm, it is the third cause of sudden death in the United States. The overall mortality rate is about 80% in countries with systematic and compulsory evaluation of death cause. This is due to the fact that substantial intra-abdominal hemorrhage is often accompanied by delays in transport and diagnoses, and the need for emergency surgery in elderly patients that frequently have significant renal and cardiopulmonary comorbidity. It is suggested that the formation and expansion of the AAA are accompanied by wall stress increasing and / or decreasing in the tissue capacity to withstand this stress. The rupture occurs when the wall stress exceed the stress the tissue can accept. The risk of rupture increases with aneurysm expansion, wall stress increasing and it is exacerbated when associated with arterial hypertension. In the present work, morphological data from thoracic region of the patient was acquired by using multi-slice CT (Computed Tomography). These DICOM images had been treated to select only the interest region, getting a three-dimensional infra-renal aortic and iliac model. Then, it was made a physical model by using rapid prototyping. This model was used for in vitro experimentation in a computer controlled mock system, in which it is possible to replicate physiological and pathological characteristics of human being cardiovascular system. Some parameters such as pressure, flow, temperature, vascular resistance and compliance can be reproduced by the use of a mock circulatory system. These parameters were used as initial boundary conditions in order to calibrate a computational model. It was adopted normotensive and hypertensive patterns and computational and experimental results were analyzed and compared. The paper proposes a methodology which allows the acquisition of anatomical and hemodynamic data on the vessel segment affected by the pathology, with the goal of providing additional information in the diagnosis of aortic aneurysm.

<p>By applying a segmentation procedure to two different sets of computed tomography scans, two geometrical models of the abdominal aorta, containing one inlet and two outlets have been constructed. One of these depicts a healthy blood vessel while the other displays one afflicted with a Abdominal Aortic Aneurysm. </p><p>After inputting these geometries into the computational dynamics software FLUENT, six simulations of laminar, stationary flow of a fluid that was assumed to be Newtonian were performed. The mass flow rate across the model outlet boundaries was varied for the different simulations to produce a basis for a parameter analysis study. </p><p>The segmentation data was also used as input data to a surface description procedure which produced not only the surface itself, but also the first and second directional derivatives in every one of its defining spatial data points. These sets of derivatives were followingly applied in an additional procedure that calculated values of Gaussian curvature. </p><p>A parameter variance analysis was carried out to evaluate the performance of the surface generation procedure. An array of resultant surfaces and surface directional derivatives were obtained. Values of Gaussian curvature were calculated in the defining spatial data points of a few selected surfaces. </p><p>The curvature values of a selected data set were visualized through a contour plot as well as through a surface map. Comparisons between the curvature surface map and one wall shear stress surface map were made.</p>

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies. Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis. Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.

Crossing of stent graft limbs during endovascular aneurysm repair (EVAR) is often used to assist cannulation and prevent graft kinking when the aortic bifurcation is widely splayed. Little has been reported about the implications of cross-limb EVAR, especially in comparison to conventional EVAR. Using computational fluid dynamics, this work numerically examines the hemodynamic differences between these two out-of-plane stent graft configurations against a planar configuration commonly found in literature. Predicted values of displacement force, wall shear stress, and oscillatory shear index were similar between the out-of-plane configurations. The planar configuration predicted similar wall shear stress values, but significantly lower displacement forces than the out-of-plane configurations. These results suggest that the hemodynamic safety of cross-limb EVAR is comparable to conventional EVAR. However, a study of clinical outcomes may reveal reduced thrombosis incidence and long-term structural implications for the stent graft in cross-limb EVAR.

Crossing of stent graft limbs during endovascular aneurysm repair (EVAR) is often used to assist cannulation and prevent graft kinking when the aortic bifurcation is widely splayed. Little has been reported about the implications of cross-limb EVAR, especially in comparison to conventional EVAR. Using computational fluid dynamics, this work numerically examines the hemodynamic differences between these two out-of-plane stent graft configurations against a planar configuration commonly found in literature. Predicted values of displacement force, wall shear stress, and oscillatory shear index were similar between the out-of-plane configurations. The planar configuration predicted similar wall shear stress values, but significantly lower displacement forces than the out-of-plane configurations. These results suggest that the hemodynamic safety of cross-limb EVAR is comparable to conventional EVAR. However, a study of clinical outcomes may reveal reduced thrombosis incidence and long-term structural implications for the stent graft in cross-limb EVAR.

By applying a segmentation procedure to two different sets of computed tomography scans, two geometrical models of the abdominal aorta, containing one inlet and two outlets have been constructed. One of these depicts a healthy blood vessel while the other displays one afflicted with a Abdominal Aortic Aneurysm. After inputting these geometries into the computational dynamics software FLUENT, six simulations of laminar, stationary flow of a fluid that was assumed to be Newtonian were performed. The mass flow rate across the model outlet boundaries was varied for the different simulations to produce a basis for a parameter analysis study. The segmentation data was also used as input data to a surface description procedure which produced not only the surface itself, but also the first and second directional derivatives in every one of its defining spatial data points. These sets of derivatives were followingly applied in an additional procedure that calculated values of Gaussian curvature. A parameter variance analysis was carried out to evaluate the performance of the surface generation procedure. An array of resultant surfaces and surface directional derivatives were obtained. Values of Gaussian curvature were calculated in the defining spatial data points of a few selected surfaces. The curvature values of a selected data set were visualized through a contour plot as well as through a surface map. Comparisons between the curvature surface map and one wall shear stress surface map were made.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease with no available pharmacological treatment. AAA formation reduces the structural integrity of the vessel and increases the susceptibility to rupture. The inflammatory response within human aneurysmal tissue is characterized by increased expression of cyclooxygenase-2 (COX-2). Similarly, in a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, we have shown that COX-2 expression in the abdominal aortic smooth muscle layer increases early in the development of the disease. Furthermore, genetic or pharmacological inactivation of COX-2 prior to disease initiation reduces AAA incidence. The current study utilized nonhyperlipidemic mice to determine the effectiveness of COX-2 inhibition initiated after AAA formation. COX-2 inhibitor treatment was initiated 5 days after beginning the AngII infusion, a time-point where significant aneurysmal pathology is observed. COX-2 inhibition with celecoxib significantly reduced the incidence as well as severity of AAAs as compared to the control group. Celecoxib treatment also protected the mice from aortic rupture and death. AAA development is characterized by degradation of the aortic smooth muscle layer with loss of the contractile phenotype. We found that the effectiveness of celecoxib was associated with significantly increased mRNA expression of alpha-actin, SM22alpha and desmin, all of which are markers of a differentiated smooth muscle cell phenotype. Celecoxib treatment also decreased mRNA expression of a marker of dedifferentiated smooth muscle (hyaluronic acid synthase 2). We also examined the role of altered expression of COX-2 in the increased susceptibility of the abdominal segment to AAA formation. We found a prolonged and greater induction of COX-2 in the abdominal aortic smooth muscle layer in contrast to a transient induction of COX-2 in the other regions of the aorta throughout disease progression. Overall, these findings suggest that COX-2 plays an important role in AAA development in mice, and COX-2 inhibition with celecoxib attenuates progression of aneurysm development by maintaining a differentiated phenotype in abdominal aortic smooth muscle cells.