Use of Nanoparticles As Contrast Agents for the Functional and Molecular Imaging of Abdominal Aortic Aneurysm

Emeto, Theophilus I.; Alele, Faith; Smith, Amy M.; Smith, Felicity M.; Dougan, Tammy; Golledge, Jonathan

doi:10.3389/fcvm.2017.00016

Cited by 11 publications

(5 citation statements)

References 76 publications

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“…Nanoparticle-based PGG delivery can be employed to quantify inflammatory events in vascular tissue pathologies such as AAA, atherosclerosis, etc. 43 Vyavahare et al . have used PGG-laden nanoparticle delivery extensively in small animal models.…”

Section: Current Issues With Pgg Administrationmentioning

confidence: 99%

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

et al. 2018

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Pentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g., oral, intravenous and endovascular route, intraperitoneal route, subcutaneous route, and nanoparticle based delivery and microbubble-based delivery), and its potential therapeutic role in vascular diseases such as abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA suppression and prevention has been demonstrated to be effective only in the calcium chloride rat AAA model. Therefore, in this critical review we address the challenges that lie ahead for the clinical translation of PGG as an AAA growth suppressor.

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Section: Current Issues With Pgg Administrationmentioning

confidence: 99%

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

et al. 2018

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“…Many AAAs remain asymptomatic and only incidentally undergo detection through abdominal imaging such as ultrasonography, computed tomography angiography, and magnetic resonance imaging ( 1 ). Despite many efforts to establish predictive or diagnostic imaging techniques ( 5 ), circulating biomarkers ( 6 ), or disease features such as intraluminal thrombus (ILT) ( 7 ) for indication of rupture-prone aneurysms, none have proven to be sufficiently robust to be implemented in clinical practice. No medical approaches to reducing AAA expansion have been validated, rather, once an aneurysm diameter has reached an established “threshold” [4.5–5.0 cm for women and 5.5 cm for men ( 8 )], the only treatment option involves surgical repair.…”

Section: Introductionmentioning

confidence: 99%

Identifying novel mechanisms of abdominal aortic aneurysm via unbiased proteomics and systems biology

Morgan

Lee

Halu

et al. 2022

Front. Cardiovasc. Med.

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BackgroundAbdominal aortic aneurysm (AAA), characterized by a continued expansion of the aorta, leads to rupture if not surgically repaired. Mice aid the study of disease progression and its underlying mechanisms since sequential studies of aneurysm development are not feasible in humans. The present study used unbiased proteomics and systems biology to understand the molecular relationship between the mouse models of AAA and the human disease.Methods and resultsAortic tissues of developing and established aneurysms produced by either angiotensin II (AngII) infusion in Apoe−/− and Ldlr−/− mice or intraluminal elastase incubation in wildtype C57BL/6J mice were examined. Aortas were dissected free and separated into eight anatomical segments for proteomics in comparison to their appropriate controls. High-dimensional proteome cluster analyses identified site-specific protein signatures in the suprarenal segment for AngII-infused mice (159 for Apoe−/− and 158 for Ldlr−/−) and the infrarenal segment for elastase-incubated mice (173). Network analysis revealed a predominance of inflammatory and coagulation factors in developing aneurysms, and a predominance of fibrosis-related pathways in established aneurysms for both models. To further substantiate our discovery platform, proteomics was performed on human infrarenal aortic aneurysm tissues as well as aortic tissue collected from age-matched controls. Protein processing and inflammatory pathways, particularly neutrophil-associated inflammation, dominated the proteome of the human aneurysm abdominal tissue. Aneurysmal tissue from both mouse and human had inflammation, coagulation, and protein processing signatures, but differed in the prevalence of neutrophil-associated pathways, and erythrocyte and oxidative stress-dominated networks in the human aneurysms.ConclusionsIdentifying changes unique to each mouse model will help to contextualize model-specific findings. Focusing on shared proteins between mouse experimental models or between mouse and human tissues may help to better understand the mechanisms for AAA and establish molecular bases for novel therapies.

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“…In associated human studies, USPIO- enhanced MRI has also been reported to enable successful visualization of severe inflammation within AAAs. The authors reported that patients with significant mural uptake of USPIO had a threefold higher AAAs growth rate (measured over 6 months) compared to those with no or non-specific USPIO uptake 33 . Degradation of elastic fibers was related to the development of the aneurysm.…”

Section: Discussionmentioning

confidence: 99%

Identification of type IV collagen exposure as a molecular imaging target for early detection of thoracic aortic dissection

Zhang

et al. 2018

Theranostics

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Thoracic aortic dissection (TAD) is an aggressive and life-threatening vascular disease and there is no effective means of early diagnosis of dissection. Type IV collagen (Col-IV) is a major component of the sub-endothelial basement membrane, which is initially exposed followed by endothelial injury as early-stage event of TAD. So, we want to build a noninvasive diagnostic method to detect early dissection by identifying the exposed Col-IV via MRI.Methods: Col-IV-targeted magnetic resonance/ fluorescence dual probe (Col-IV-DOTA-Gd-rhodamine B; CDR) was synthesized by amide reaction and coordination reaction. Flow cytometry analysis was used to evaluate the cell viability of SMC treated with CDR and fluorescence assays were used to assess the Col-IV targeting ability of CDR in vitro. We then examined the sensitivity and specificity of CDR at different stages of TAD via MRI and bioluminescence imaging in vivo.Results: The localization of Col-IV (under the intima) was observed by histology images. CDR bound specifically to Col-IV-expressing vascular smooth muscle cells and BAPN-induced dissected aorta. The CDR signal was co-detected by magnetic resonance imaging (MRI) and bioluminescence imaging as early as 2 weeks after BAPN administration (pre-dissection stage). The ability to detect rupture of dissected aorta was indicated by a strong normalized signal enhancement (NSE) in vivo. Moreover, NSE was negatively correlated with the time of dissection rupture after BAPN administration (r2 = 0.8482).Conclusion: As confirmed by in vivo studies, the CDR can identify the exposed Col-IV in degenerated aorta to monitor the progress of aortic dissection from the early stage to the rupture via MRI. Thus, CDR-enhanced MRI proposes a potential method for dissection screening, and for monitoring disease progression and therapeutic response.

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Use of Nanoparticles As Contrast Agents for the Functional and Molecular Imaging of Abdominal Aortic Aneurysm

Cited by 11 publications

References 76 publications

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

Identifying novel mechanisms of abdominal aortic aneurysm via unbiased proteomics and systems biology

Identification of type IV collagen exposure as a molecular imaging target for early detection of thoracic aortic dissection

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