Lymphangiogenesis in abdominal aortic aneurysm

Scott, Daniel; Allen, Chris; Honstvet, Christopher A.; Hanby, AM; Hammond, Christopher J; Johnson, Anne B.; Perry, Sarah L.; Jones, Pamela F.

doi:10.1002/bjs.9128

Cited by 12 publications

(14 citation statements)

References 48 publications

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“…One important advantage of targeting angiogenesis is that rapid, persistent and specific targeting can be achieved with different probes, which endows an excellent efficiency and imaging contrast. The endothelial cells of newly formed vessels express high levels of CD105, also known as endoglin, on their surfaces (17). We have previously demonstrated the efficacy of a CD105 targeted antibody, TRC105, for in vivo imaging of angiogenesis (18–21).…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of Abdominal Aortic Aneurysm with ⁶⁴Cu-Labeled Anti-CD105 Antibody Fab Fragment

et al. 2015

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The critical challenge in abdominal aortic aneurysm (AAA) research is the accurate diagnosis and assessment of AAA progression. Angiogenesis is a pathological hallmark of AAA, and CD105 is highly expressed on newly formed vessels. Our goal was to use 64Cu-labeled anti-CD105 antibody Fab fragment for noninvasive assessment of angiogenesis in the aortic wall in a murine model of AAA. Methods Fab fragment of TRC105, a mAb that specifically binds to CD105, was generated by enzymatic papain digestion and conjugated to NOTA for 64Cu-labeling. Binding affinity/specificity of NOTA-TRC105-Fab was evaluated by flow cytometry and various ex vivo studies. BALB/c mice were anesthetized and treated with calcium phosphate to induce AAA, which underwent weekly PET scans using 64Cu-NOTA-TRC105-Fab. Biodistribution and autoradiography studies were also performed to confirm the accuracy of PET results. Results NOTA-TRC105-Fab exhibited high purity and specifically bound to CD105 in vitro. Uptake of 64Cu-NOTA-TRC105-Fab increased from a control level of 3.4 ± 0.1 to 9.5 ± 0.4 %ID/g at 6 h p.i. on Day 5, and decreased to 7.2 ± 1.4 %ID/g on Day 12 which correlated well with biodistribution and autoradiography studies (i.e. much higher tracer uptake in AAA than normal aorta). Of note, enhanced AAA contrast was achieved, due to the minimal background in the abdominal area of mice. Degradation of elastic fibers and highly expressed CD105 were observed in ex vivo studies. Conclusion 64Cu-NOTA-TRC105-Fab cleared rapidly through kidneys, which enabled noninvasive PET imaging of the aorta with enhanced contrast and showed increased angiogenesis (CD105 expression) during AAA. 64Cu-NOTA-TRC105-Fab PET may potentially be used for future diagnosis and prognosis of AAA.

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Section: Introductionmentioning

confidence: 99%

PET Imaging of Abdominal Aortic Aneurysm with ⁶⁴Cu-Labeled Anti-CD105 Antibody Fab Fragment

et al. 2015

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“…Abdominal aortic aneurysm (AAA) is a progressive condition affecting mainly older men . Aneurysms typically grow by 2 mm per year and once the size exceeds 55 mm there is an increased risk of rupture, when patients are considered for open (OAR) or endovascular repair (EVAR) .…”

Section: Introductionmentioning

confidence: 99%

Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm

Bailey

Aggarwal

Bridge

et al. 2015

Journal of Thrombosis and Haemostasis

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Scott DJA, Ajjan RA. Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm. J Thromb Haemost 2015; 13: 795-801.Summary. Objective: Thrombotic changes in fibrin networks contribute to increased cardiovascular risk in patients with abdominal aortic aneurysm (AAA). Given that aspirin modulates the fibrin network, we aimed to determine if aspirin therapy is associated with changes in ex-vivo fibrin clot characteristics in AAA patients and also conducted an exploratory analysis of 5-year mortality in these individuals. Methods: We recruited 145 male patients, divided into controls (aortic diameter < 3 cm, n = 49), AAA not taking aspirin (AAAÀAsp, n = 50) and AAA on 75 mg day À1 aspirin (AAA+Asp, n = 46), matched for aneurysm size. Characteristics of clots made from plasma and plasma-purified fibrinogen were investigated using turbidimetric analysis, permeation studies, and confocal and electron microscopy. Plasma fibrinogen, D-dimer and inflammatory marker levels were also measured. Results: Maximum absorbance (MA) of plasma clots from controls was lower than that of AAA patients not on aspirin (AAAÀAsp) at 0.30 AE 0.01 and 0.38 AE 0.02 au, respectively (P = 0.002), whereas aspirintreated subjects had MA similar to controls (0.31 AE 0.02 P = 0.9). Plasma clot lysis time displayed an identical pattern at 482 AE 15, 597 AE 24 and 517 AE 27 s for control, AAAÀAsp and AAA+Asp (P = 0.001 and P = 0.8). The lysis time of clots made from purified fibrinogen of AAAÀAsp was longer than that of AAA+Asp patients (756 AE 47 and 592 AE 52 s, respectively; P = 0.041). Permeation studies and confocal and electron microscopy showed increased clot density in AAAÀAsp compared with the AAA+Asp group. Mortality in AAAÀAsp and AAA+Asp was similar, despite increased cardiovascular risk in the latter group, and both exhibited higher mortality than controls. Conclusion: Aspirin improves fibrin clot characteristics in patients with AAA, which may have important clinical implications.

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“…A study by Scott et al [47] attempted to research the relationship between inflammation and neovascularization in AAA tissue. The results showed that the aneurysm wall contained high levels of inflammatory infiltrate, while microvascular densities of blood ( P < 0.001) and lymphatic ( P = 0.003) vessels were significantly increased in AAA samples compared with controls.…”

Section: Resultsmentioning

confidence: 99%

“…Vascularity as expressed by positive staining for CD31, CD105, and D2-40 correlated positively with inflammation, while increased VEGFR-3 and VEGF-A expression was observed within inflammatory areas of AAAs. These results suggest lymphatic vessel involvement in AAA disease, associated with the extent of inflammation [47]. …”

Section: Resultsmentioning

confidence: 99%

Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions

Moris

Mantonakis

Avgerinos

et al. 2014

BioMed Research International

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Abdominal aortic aneurysm (AAA) is a prevalent and potentially life-threatening disease. Early detection by screening programs and subsequent surveillance has been shown to be effective at reducing the risk of mortality due to aneurysm rupture. The aim of this review is to summarize the developments in the literature concerning the latest biomarkers (from 2008 to date) and their potential screening and therapeutic values. Our search included human studies in English and found numerous novel biomarkers under research, which were categorized in 6 groups. Most of these studies are either experimental or hampered by their low numbers of patients. We concluded that currently no specific laboratory markers allow screeing for the disease and monitoring its progression or the results of treatment. Further studies and studies in larger patient groups are required in order to validate biomarkers as cost-effective tools in the AAA disease.

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Lymphangiogenesis in abdominal aortic aneurysm

Abstract: These findings demonstrated lymphatic vessel involvement in end-stage AAA disease, which was associated with the degree of inflammation, and confirmed the involvement of neovascularization.

Cited by 12 publications

References 48 publications

PET Imaging of Abdominal Aortic Aneurysm with ⁶⁴Cu-Labeled Anti-CD105 Antibody Fab Fragment

PET Imaging of Abdominal Aortic Aneurysm with ⁶⁴Cu-Labeled Anti-CD105 Antibody Fab Fragment

Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm

Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions

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Lymphangiogenesis in abdominal aortic aneurysm

Abstract: These findings demonstrated lymphatic vessel involvement in end-stage AAA disease, which was associated with the degree of inflammation, and confirmed the involvement of neovascularization.

Cited by 12 publications

References 48 publications

PET Imaging of Abdominal Aortic Aneurysm with 64Cu-Labeled Anti-CD105 Antibody Fab Fragment

PET Imaging of Abdominal Aortic Aneurysm with 64Cu-Labeled Anti-CD105 Antibody Fab Fragment

Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm

Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions

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PET Imaging of Abdominal Aortic Aneurysm with ⁶⁴Cu-Labeled Anti-CD105 Antibody Fab Fragment

PET Imaging of Abdominal Aortic Aneurysm with ⁶⁴Cu-Labeled Anti-CD105 Antibody Fab Fragment