RESUMO
Aneurysm formation occurs most frequently as abdominal aortic aneurysm (AAA), but is also seen in other localizations like thoracic or peripheral aneurysm. While initial mechanisms for aneurysm induction remain elusive, observations from AAA samples show transmural inflammation with proteolytic imbalance and repair mechanisms triggered by the innate immune system. However, limited knowledge exists about aneurysm pathology, especially for others than AAA. We compared 42 AAA, 15 popliteal, 3 ascending aortic, five iliac, two femoral, two brachial, one visceral and two secondary aneurysms to non-aneurysmatic controls by histologic analysis, immunohistochemistry and cytokine expression. Muscular and elastic type arteries show a uniform way of aneurysm formation. All samples show similar morphology. The changes compared to controls are distinct and include matrix remodeling with smooth muscle cell phenotype switch and angiogenesis, adventitial lymphoid cell accumulation and M1 macrophage homing together with neutrophil inflammation. Inflammatory cytokines are up-regulated accordingly. Comparative analysis of different disease entities can identify characteristic pathomechanisms. The phenotype of human advanced aneurysm disease is observed for elastic and muscular type arteries, does not differ between disease localizations and might, thus, be a unique response of the vasculature to the still unknown trigger of aneurysm formation.
Assuntos
Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Artérias/metabolismo , Artérias/patologia , Aneurisma da Aorta Abdominal/cirurgia , Citocinas/biossíntese , Citocinas/metabolismo , Humanos , Imuno-HistoquímicaRESUMO
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease. METHODS: Tissue samples from AAA and popliteal artery aneurysm patients were examined by histomorphologic analysis, immunohistochemistry, Western blot, and polymerase chain reaction. The results were correlated with clinical data such as aneurysm diameter and laboratory results. RESULTS: The morphology of human AAA vessel wall probes varies tremendously based on the grade of inflammation. This correlates with increasing intima/media thickness and upregulation of the vascular endothelial growth factor cascade but not with any clinical parameter or the aneurysm diameter. The phenotypic switch of vascular smooth muscle cells occurred regardless of the inflammatory state and expressional changes of the transcription factors Kruppel-like factor-4 and transforming growth factor-ß lead to differential protein localization in aneurysmal compared with control arteries. These changes were in similar manner also observed in samples from popliteal artery aneurysms, which, however, showed a more homogenous phenotype. CONCLUSIONS: Heterogeneity of AAA vessel walls based on inflammatory morphology does not correlate with AAA diameter yet harbors specific implications for basic research and possible aneurysm detection.
Assuntos
Aneurisma/patologia , Aneurisma da Aorta Abdominal/patologia , Desdiferenciação Celular , Inflamação/patologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Aneurisma/diagnóstico por imagem , Aneurisma/metabolismo , Proteínas Angiogênicas/análise , Aorta Abdominal/química , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/metabolismo , Aortografia/métodos , Biomarcadores/análise , Angiografia por Tomografia Computadorizada , Dilatação Patológica , Matriz Extracelular/química , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/análise , Humanos , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Mediadores da Inflamação/análise , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/análise , Músculo Liso Vascular/química , Miócitos de Músculo Liso/química , Fenótipo , Artéria Poplítea/química , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/patologia , Fator de Crescimento Transformador beta/análise , Remodelação VascularRESUMO
BACKGROUND: The whole school, whole community, whole child (WSCC) model suggests wellness councils, ongoing review of wellness policy, and a plan for evaluating set objectives are some of the key features needed to support school wellness infrastructure. This study explored the relationship between implementation of these infrastructure features and overall school wellness environment assessment scores among a sampling of Pennsylvania schools. METHODS: The Healthy Champions program provides Pennsylvania schools an opportunity to self-assess their wellness environments across several school wellness topics. Staff enrolled their school in the program by completing a self-report electronic assessment. Enrollment data from the 2020/2021 program year were analyzed using the Kruskal-Wallis test and linear fixed model to identify the impact of varied implementation levels across 3 wellness infrastructure activities. Interactions between these variables and overall assessment score were also analyzed. RESULTS: Of the 645 Pennsylvania schools enrolled and analyzed, we observed higher mean wellness environment assessment scores (∆ 0.74 95% CI 0.40-1.07; p < 0.001) among schools that reported some frequency of all 3 wellness infrastructure activities, compared to schools that reported no frequency for the activities. IMPLICATIONS: Schools with existing policies and practices related to the 3 wellness infrastructure activities should consider the degree of implementation to best support overall wellness in their school setting. Additional research to explore implementation barriers and supports is needed. CONCLUSIONS: Analyses indicated that overall wellness environment assessment scores are impacted by implementation thresholds for wellness council meeting frequency, revision of wellness policy, and review of student health promotion objectives.