scholarly journals Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of β-aminopropionitrile-induced Aortic Aneurysm and Dissection

Author(s):  
Brittany O. Aicher ◽  
Subhradip Mukhopadhyay ◽  
Xin Lu ◽  
Selen C. Muratoglu ◽  
Dudley K. Strickland ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Guanglang Zhu ◽  
Huiying Sun ◽  
Jiannan Wang ◽  
Zhiqing Zhao ◽  
Junmin Bao ◽  
...  

Objectives. The aim of this study was to evaluate the potential of microcomputed tomography (micro-CT) using the intravascular contrast agent ExiTron nano 12000 for aorta imaging and monitoring the dynamic changing process of the aorta in mouse models with aortic aneurysm and dissection. Materials and Methods. Experiments were performed on healthy mice and mice with aortic dissection. Mice that were developing aortic dissection and healthy mice underwent micro-CT imaging after injection of ExiTron nano 12000. Time-dependent signal enhancement (at 1, 2, 3, 6, and 12 hours after intravenous injection of the contrast agent, respectively) in the aorta of healthy mice was measured to confirm the optimal imaging time of aorta. Various contrast agent doses (70, 100, and 150 μl per 25 g mouse, respectively) were investigated to determine the optimal required dose for imaging of the aorta. The mice were scanned with micro-CT at 1, 14, and 28 days after onset of aneurysm and dissection to monitor the dynamic changing process of the aorta. Mouse aortas were stained with hematoxylin and eosin staining, and the diameter of the aorta was measured and compared with those obtained by micro-CT. Results. Time-dependent signal enhancement in the aorta shows that the contrast agent has a long blood half-life of 6 hours, with a peak enhancement at 2 hours after injection. Injection of 100 μl ExiTron nano 12000 per 25 g mouse allows for effective visualization of the aorta. Micro-CT combined with contrast agent can monitor the changing process of the aorta in the mouse model of aortic aneurysm and dissection dynamically. The values of the diameter of the aortas obtained from the in vivo micro-CT imaging were compared with those obtained from histology and showed a significant correlation (R2 = 0.96). Conclusions. These data demonstrate that in vivo micro-CT is an accurate and feasible technique to detect aortic aneurysm or dissection in a mouse model, and the micro-CT technique using the innovative contrast agent ExiTron nano 12000 allows for monitoring various processes dynamically such as aortic remodeling in longitudinal studies.


2020 ◽  
Vol 25 (4) ◽  
pp. 364-376 ◽  
Author(s):  
Sheng Le ◽  
Hao Zhang ◽  
Xiaofan Huang ◽  
Shu Chen ◽  
Jia Wu ◽  
...  

Background: The development of thoracic aortic aneurysm and dissection (TAAD) is mediated by inflammasome activation, which exacerbates the secretion of pro-inflammatory cytokines, chemokines, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS). The glycolytic enzyme pyruvate kinase M2 (PKM2) has shown a protective role against various disorders with an inflammatory basis, such as sepsis, tumorigenesis, and diabetic nephropathy. However, its potential role in TAAD has not been investigated so far. Approach and Results: We analyzed aortic tissues from TAAD patients and the β-aminopropionitrile fumarate (BAPN)–induced mouse model of TAAD and observed elevated levels of PKM2 in the aortic lesions of both. Treatment with the PKM2 activator TEPP-46 markedly attenuated the progression of TAAD in the mouse model as demonstrated by decreased morbidity and luminal diameter of the aorta. In addition, the thoracic aortas of the BAPN-induced mice showed reduced monocytes and macrophages infiltration and lower levels of IL-1β, MMPs, and ROS when treated with TEPP-46. Furthermore, TEPP-46 treatment also suppressed the activation of the NOD-like receptor (NLR) family and pyrin domain–containing protein 3 (NLRP3) inflammasome by downregulating p-STAT3 and HIF1-α. Conclusion: Pyruvate kinase M2 plays a protective role in TAAD development, and its activation is a promising therapeutic strategy against the progression of TAAD.


2018 ◽  
Vol 132 (12) ◽  
pp. 1253-1256 ◽  
Author(s):  
Clinton S. Robbins ◽  
John S. Byrne

The pathogenesis of thoracic aortic aneurysm and dissection (TAAD) is complex and incompletely understood. The hallmarks of the disease process are aortic inflammatory cell infiltration and protease mediated elastic fiber disruption. In a study recently published in Clinical Science (2018) 132 (6), 655–668), Liu et al. explore the mechanism through which aortic vascular smooth cells and macrophages participate in TAAD using a mouse model. The authors propose that interleukin-3 (IL-3) released from aortic vascular smooth cells is central to the disease process. IL-3 stimulated matrix metalloproteinase 12 (MMP12) release from macrophages via mitogen activated protein kinase pathways. MMP12 is a protease known to be involved in both aortic aneurysm and dissection. IL-3 knockout mice had significantly reduced aortic wall MMP12, and reduced protease activity. This was associated with protection against TAAD.


2021 ◽  
Author(s):  
Francesca Ravanetti ◽  
Erica Ferrini ◽  
Luisa Ragionieri ◽  
Zahra Khalajzeyqami ◽  
Maria Nicastro ◽  
...  

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by an excessive production and accumulation of collagen in the skin and internal organs often associated with interstitial lung disease (ILD). The unknown pathogenetic mechanisms of SSc-ILD and the lack of animal models mimicking the features of the human disease contribute to create a gap between the selection of antifibrotic drug candidates and effective therapies. Nintedanib (NINT) was used as a tool compound to validate the pharmacological response either on lung or skin fibrosis in a SSc-ILD mouse model. The model is based on the continuous infusion of bleomycin (BLM) by osmotic minipumps for 1 week in the C57BL/6 female mice. Longitudinal Micro-CT analysis highlighted a significant slowdown in lung fibrosis progression after NINT treatment, then confirmed by histology. However, no significant effect was observed on lung hydroxyproline content, inflammatory infiltrate and skin lipoatrophy. The modest pharmacological effect reported reflects the clinical outcome, lighting up the reliability of this model to serve as secondary screening to profile the best clinical drug candidates. Moreover, we have underlined the pivotal role of Micro-CT imaging, together describing the relevant readouts and the importance of their validation prior to use for drug discovery.


2015 ◽  
Vol 6 ◽  
Author(s):  
Chan Gao ◽  
Brian P. Chen ◽  
Michael B. Sullivan ◽  
Jasmine Hui ◽  
Jean A. Ouellet ◽  
...  
Keyword(s):  
Micro Ct ◽  

Author(s):  
Melissa R. Requist ◽  
Yantarat Sripanich ◽  
Tim Rolvien ◽  
Amy L. Lenz ◽  
Alexej Barg

Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 1995
Author(s):  
Mirko Sinico ◽  
Suraj Dinkar Jadhav ◽  
Ann Witvrouw ◽  
Kim Vanmeensel ◽  
Wim Dewulf

Recently, the use of novel CuCr1 surface-modified powder for reliable laser powder-bed fusion (LPBF) manufacturing has been proposed, enabling a broader LPBF processing window and longer powder storage life. Nevertheless, virgin CuCr1 powder is also LPBF processable, on the condition that a high-energy density is employed. In this work, we compare two dense specimens produced from virgin and surface-modified CuCr1 powder. Furthermore, a third sample fabricated from surface-modified powder is characterized to understand an abnormal porosity content initially detected through Archimedes testing. Utilizing high-resolution micro-CT scans, the nature of the defects present in the different samples is revealed. Pores are analyzed in terms of size, morphology and spatial distribution. The micro-CT data reveal that the virgin CuCr1 dense specimen displays keyhole pores plus pit cavities spanning multiple layer thicknesses. On the other hand, the sample fabricated with the surface-modified CuCr1 powder mainly contains small and spherical equi-distributed metallurgical defects. Finally, the CT analysis of the third specimen reveals the presence of a W contamination, favoring lack-of-fusion pores between subsequent LPBF layers. The LPBF melting mode (keyhole or conductive), the properties of the material, and the potential presence of contaminants are connected to the different porosity types and discussed.


2016 ◽  
Vol 22 (S3) ◽  
pp. 1196-1197 ◽  
Author(s):  
Jeffrey R Tonniges ◽  
Ben Albert ◽  
Edward Calomeni ◽  
Chetan Hans ◽  
Gunjan Agarwal

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