RESUMO
Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi, here we used intravital microscopy (IVM) to investigate microcirculatory alterations in the hamster cheek pouch (HCP) infected by green fluorescent protein-expressing T. cruzi (GFP-T. cruzi). IVM performed 3 days post-infection (3 dpi) consistently showed increased baseline levels of plasma extravasation. Illustrating the reciprocal benefits that microvascular leakage brings to the host-parasite relationship, these findings suggest that intracellular amastigotes, acting from inside out, stimulate angiogenesis while enhancing the delivery of plasma-borne nutrients and prosurvival factors to the infection foci. Using a computer-based analysis of images (3 dpi), we found that proangiogenic indexes were positively correlated with transcriptional levels of proinflammatory cytokines (pro-IL1ß and IFN-γ). Intracellular GFP-parasites were targeted by delaying for 24 h the oral administration of the trypanocidal drug benznidazole. A classification algorithm showed that benznidazole (>24 h) blunted angiogenesis (7 dpi) in the HCP. Unbiased proteomics (3 dpi) combined to pharmacological targeting of chymase with two inhibitors (chymostatin and TY-51469) linked T. cruzi-induced neovascularization (7 dpi) to the proangiogenic activity of chymase, a serine protease stored in secretory granules from mast cells.
RESUMO
Introdução: A reconstrução tridimensional coronária com a combinação do ultrassom intracoronário e da angiografia apresenta vantagens em relação à angiotomografia de coronárias. Objetivamos apresentara fase piloto de validação de um novo modelo de reconstrução tridimensional de artérias coronárias. Métodos: Foram utilizados exames de angiografia e ultrassom intracoronário já realizados por indicação clínica em indivíduos com suspeita ou diagnóstico de doença arterial coronária estável. O processamento das imagens, a segmentação e a reconstrução tridimensional foram realizados seguindo metodologia específica. Para fins de caracterização geométrica, foram obtidas as linhas de centro tridimensionais. Resultados: Foram reconstruídos três vasos, sendo duas artérias descendentes anteriores e uma artéria circunflexa. O volume da luz do vaso e a carga de placa global puderam ser visualizados com facilidade com a reconstrução tridimensional. A caracterização geométrica revelou aumento dos valores absolutos do comprimento, tortuosidade, curvatura e torsão, caracterizando uma maior complexidade da linha de centro da luz doente, em relação à linha de centro da membrana elástica externa. Conclusões: Essa nova metodologia, que integrou angiografia convencional e ultrassom intracoronário, aumentou a praticidade das reconstruções, com ganho em acurácia volumétrica do vaso e visualização global de aspectos-chave da doença aterosclerótica, como remodelamento e distribuição da placa.
Background: Coronary three-dimensional reconstruction with the combination of intravascular ultrasound and angiography offers advantages over computed tomography angiography of coronary arteries. The authors aimed to present the pilot phase of the validation of a new model of three-dimensional reconstruction of coronary arteries. Methods: This study used angiography and intravascular ultrasound examinations already performed by clinical indication in individuals with known or suspected stable coronary artery disease. Image processing, segmentation, and three-dimensional reconstruction were conducted following specific methodology. For geometrical characterization purposes, tridimensional center lines were obtained. Results: Three vessels were reconstructed: two left anterior descending arteries and one left circumflex artery. The vessel lumen volume and the overall plaque burden could be easily viewed with threedimensional reconstruction. The geometric characterization revealed increased absolute values of length, tortuosity, curvature, and torsion, featuring a greater complexity of the center line of the diseased lumen relative to the center line of the external elastic membrane. Conclusions: This new methodology, which integrates conventional angiography and intravascular ultrasound, has increased the practicality of the reconstructions, with a gain in volumetric accuracy of the vessel and overall visualization of key aspects of atherosclerotic disease, such as plaque remodeling and distribution.