scholarly journals Thrombospondin-1 (TSP1) Contributes to the Development of Vascular Inflammation by Regulating Monocytic Cell Motility in Mouse Models of Abdominal Aortic Aneurysm

2015 ◽  
Vol 117 (2) ◽  
pp. 129-141 ◽  
Author(s):  
Zhenjie Liu ◽  
Stephanie Morgan ◽  
Jun Ren ◽  
Qiwei Wang ◽  
Douglas S. Annis ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cell Motility ◽  
Mouse Models ◽  
Vascular Inflammation ◽  
Monocytic Cell ◽  
Abdominal Aortic ◽  
Thrombospondin 1

scholarly journals Systematic Review and Meta-Analysis of Interventions to Slow Progression of Abdominal Aortic Aneurysm in Mouse Models

2021 ◽  
Author(s):  
James Phie ◽  
Shivshankar Thanigaimani ◽  
Jonathan Golledge
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Mouse Models ◽  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Model Studies ◽  
Abdominal Aortic ◽  
Meta Analyses

Objective: There are no current effective abdominal aortic aneurysm (AAA) drug therapies. An important limitation of most preclinical studies is that they test the effect of drugs on AAA formation rather than AAA progression. The aim of this study was to systematically review AAA mouse model studies that have tested the effect of interventions in limiting the progression of preestablished AAA. Approach and Results: The literature search identified 35 studies meeting eligibility, and 30 (n=935 mice) contributed to the meta-analyses. AAAs were induced with angiotensin II (n=745 mice), calcium chloride (n=91 mice), or elastase (n=99 mice). Anti-inflammatory drugs (standardized mean difference [SMD], 1.62 [95% CI, 0.93–2.30]), protease inhibitors (SMD, 1.23 [95% CI, 0.52–1.95]), stem cells (SMD, 1.64 [95% CI, 1.05–2.24]), antiplatelet or anticoagulant drugs (SMD, 0.93 [95% CI, 0.63–1.22]), and renin-angiotensin system inhibitors (SMD, 1.45 [95% CI, 0.58–2.33]) reduced AAA diameter. Interventions initiated soon after model induction commenced were more likely to reduce AAA diameter (R 2 , 16%; P =0.007). Funnel plots suggested possible publication bias. Most studies did not report blinding or sample size calculations, and the risk of bias was considered medium or high in 20 (57%) of the 35 studies. Conclusions: There is low-quality evidence that a range of drugs are effective in limiting AAA progression when administered early after AAA induction in mouse models. Some of these drugs, such as antiplatelet and renin-angiotensin system inhibitors, have been reported to be ineffective in clinical trials.

scholarly journals A preclinical ultrasound method for the assessment of vascular disease progression in murine models

Ultrasound ◽  
2018 ◽  
Vol 27 (2) ◽  
pp. 85-93
Author(s):  
Justyna Janus ◽  
Baris Kanber ◽  
Wadhah Mahbuba ◽  
Charlotte Beynon ◽  
Kumar V Ramnarine ◽  
...  
Keyword(s):  
Image Processing ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Disease ◽  
Mouse Models ◽  
Murine Models ◽  
Analysis Method ◽  
Manual Analysis ◽  
Abdominal Aortic ◽  
Automatic Image Processing

Introduction The efficacy of preclinical ultrasound at providing a quantitative assessment of mouse models of vascular disease is relatively unknown. In this study, preclinical ultrasound was used in combination with a semi-automatic image processing method to track arterial distension alterations in mouse models of abdominal aortic aneurysm and atherosclerosis. Methods Longitudinal B-mode ultrasound images of the abdominal aorta were acquired using a preclinical ultrasound scanner. Arterial distension was assessed using a semi-automatic image processing algorithm to track vessel wall motion over the cardiac cycle. A standard, manual analysis method was applied for comparison. Results Mean arterial distension was significantly lower in abdominal aortic aneurysm mice between day 0 and day 7 post-onset of disease (p < 0.01) and between day 0 and day 14 (p < 0.001), while no difference was observed in sham control mice. Manual analysis detected a significant decrease (p < 0.05) between day 0 and day 14 only. Atherosclerotic mice showed alterations in arterial distension relating to genetic modification and diet. Arterial distension was significantly lower (p < 0.05) in Ldlr−/− (++/−−) mice fed high-fat western diet when compared with both wild type (++/++) mice and Ldlr−/− (++/−−) mice fed chow diet. The manual method did not detect a significant difference between these groups. Conclusions Arterial distension can be used as an early marker for the detection of arterial disease in murine models. The semi-automatic analysis method provided increased sensitivity to differences between experimental groups when compared to the manual analysis method.

scholarly journals Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dilyana B. Mangarova ◽  
Julia Brangsch ◽  
Azadeh Mohtashamdolatshahi ◽  
Olaf Kosch ◽  
Hendrik Paysen ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Murine Model ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Vascular Inflammation ◽  
Magnetic Particle Imaging ◽  
Abdominal Aortic ◽  
Particle Imaging

scholarly journals High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice

2017 ◽  
Vol 131 (12) ◽  
pp. 1261-1281 ◽  
Author(s):  
Smriti Murali Krishna ◽  
Sai Wang Seto ◽  
Roby Jose ◽  
Jiaze Li ◽  
Joseph Moxon ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Ex Vivo ◽  
High Serum ◽  
Matricellular Protein ◽  
Body Tissues ◽  
Age Related ◽  
Abdominal Aortic ◽  
Thrombospondin 1

Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman’s rho −0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40; 95% confidence interval (CI): 0.19–0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1−/−ApoE−/−, n=20) and control mice (ApoE−/−, n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1−/− ApoE−/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1−/−ApoE−/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1−/−ApoE−/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1−/−ApoE−/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.

scholarly journals ACE Inhibitors Potently Reduce Vascular Inflammation, Results of an Open Proof-Of-Concept Study in the Abdominal Aortic Aneurysm

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e111952 ◽  
Author(s):  
Kim E. Kortekaas ◽  
C. Arnoud Meijer ◽  
Jan Willem Hinnen ◽  
Ronald L. Dalman ◽  
Baohui Xu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Ace Inhibitors ◽  
Vascular Inflammation ◽  
Proof Of Concept ◽  
Concept Study ◽  
Abdominal Aortic

scholarly journals Heat shock protein 90 inhibition by 17-DMAG attenuates abdominal aortic aneurysm formation in mice

2015 ◽  
Vol 308 (8) ◽  
pp. H841-H852 ◽  
Author(s):  
Jia Qi ◽  
Ping Yang ◽  
Bing Yi ◽  
Yan Huo ◽  
Ming Chen ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Heat Shock ◽  
Aortic Aneurysm ◽  
Heat Shock Protein ◽  
Vascular Inflammation ◽  
Heat Shock Protein 90 ◽  
Ang Ii ◽  
Iκb Kinase ◽  
Abdominal Aortic ◽  
Novel Strategy

Abdominal aortic aneurysm (AAA) is a common degenerative vascular disease whose pathogenesis is associated with activation of multiple signaling pathways including Jun NH2-terminal kinases (JNK) and NF-κB. It is now well recognized that these pathways are chaperoned by the heat shock protein 90 (Hsp90), suggesting that inhibition of Hsp90 may be a novel strategy for inhibiting AAAs. The aim of this study is to investigate whether inhibition of Hsp90 by 17-DMAG (17-dimethyl-aminothylamino-17-demethoxy-geldanamycin) attenuates ANG II-induced AAA formation in mice, and, if so, to elucidate the mechanisms involved. Apolipoprotein E-null mice were infused with ANG II to induce AAA formation and simultaneously treated by intraperitoneal injection with either vehicle or 17-DMAG for 4 wk. ANG II infusion induced AAA formation in 80% of mice, which was accompanied by increased matrix metalloproteinase (MMP) activity, enhanced tissue inflammation, oxidative stress, and neovascularization. Importantly, these effects were inhibited by 17-DMAG treatment. Mechanistically, we showed that 17-DMAG prevented the formation and progression of AAA through its inhibitory effects on diverse biological pathways including 1) by blocking ANG II-induced phosphorylation of ERK1/2 and JNK that are critically involved in the regulation of MMPs in vascular smooth muscle cells, 2) by inhibiting IκB kinase expression and expression of MCP-1, and 3) by attenuating ANG II-stimulated angiogenic processes critical to AAA formation. Our results demonstrate that inhibition of Hsp90 by 17-DMAG effectively attenuates ANG II-induced AAA formation by simultaneously inhibiting vascular inflammation, extracellular matrix degradation, and angiogenesis, which are critical in the formation and progression of AAAs.

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