Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation

Alie, Nadia; Eldib, Mootaz; Fayad, Zahi A.; Mani, Venkatesh

doi:10.4137/cmc.s17063

Cited by 56 publications

(48 citation statements)

References 100 publications

(192 reference statements)

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“…To begin to address the problem of noninvasively detecting vulnerable plaques likely to rupture, several new imaging modalities aimed at targeting molecular and cellular activities have emerged (13,14). PET/CT has been explored as a technique to detect and quantify the presence of inflammation within carotid plaques (13)(14)(15)(16)(17)(18). Most PET/CT studies for atherosclerosis make use of 18 F-FDG as a contrast agent.…”

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confidence: 99%

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Withana

Saito

et al. 2016

J Nucl Med

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Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that activity-based probes (ABPs) targeting cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes can also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Methods: Macrophage-rich carotid lesions were induced in FVB mice fed on a high-fat diet by streptozotocin injection followed by ligation of the left common carotid artery. Mice with carotid atherosclerotic plaques were injected with the optical or dual-modality probes BMV109 and BMV101, respectively, via the tail vein and noninvasively imaged by optical and small-animal PET/CT at different time points. After noninvasive imaging, the murine carotid arteries were imaged in situ and ex vivo, followed by immunofluorescence staining to confirm target labeling. Additionally, human carotid plaques were topically labeled with the probe and analyzed by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunofluorescence staining to confirm the primary targets of the probe. Results: Quantitative analysis of the signal intensity from both optical and PET/CT imaging showed significantly higher levels of accumulation of BMV109 and BMV101 (P , 0.005 and P , 0.05, respectively) in the ligated left carotid arteries than the right carotid or healthy arteries. Immunofluorescence staining for macrophages in cross-sectional slices of the murine artery demonstrated substantial infiltration of macrophages in the neointima and adventitia of the ligated left carotid arteries compared with the right. Analysis of the human plaque tissues by sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed that the primary targets of the probe were cathepsins X, B, S, and L. Immunofluorescence labeling of the human tissue with the probe demonstrated colocalization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimental carotid inflammation murine model. Conclusion: We demonstrate that ABPs targeting the cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes could also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Therefore, ABPs targeting the cysteine cathepsins are potentially valuable new reagents for rapid and noninvasive imaging of atherosclerotic disease progression and plaque vulnerability.

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confidence: 99%

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Withana

Saito

et al. 2016

J Nucl Med

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“…Presence of hypertension is also related to increased oxidative stress and consequent triggering of the inflammatory process in the walls of blood vessels. 24,29,50 Hyperglycemia and development of DM are related to development of atherosclerosis via different mechanisms. One widely studied mechanism, perhaps the most studied, is that related to AGEs, which are linked with genesis of plaques, but can also accumulate in lesions.…”

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confidence: 99%

Síndrome metabólica, aterosclerose e inflamação: tríade indissociável?

et al. 2015

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Populations all over the world are increasingly inactive and are consuming increasing quantities of fats and sugars, which is generally linked to industrially processed foods. The consequences have rapidly manifest as an increase in overweight/obesity and in physiological and metabolic changes, such as the Metabolic Syndrome, which is a series of changes in glycemia, lipids and blood pressure. There is evidence of a close relationship between these changes and inflammatory processes, which can also be linked to oxidative stress. These conditions lead to the pathogenesis of vascular abnormalities or intensify metabolic processes that accompany the metabolic syndrome. The objective of this review is to compare the large number of bibliographic references that show correlations between components of the Metabolic Syndrome and increases in the mediators of inflammation. The publications reviewed were located using the Pubmed, Scopus, Lilacs and Scielo databases and the majority of the articles selected were published within the last 5 years.Keywords: metabolic syndrome ; arteriosclerosis; inflammation. ResumoObserva-se, nas populações mundiais, aumento do sedentarismo e aumento do consumo de gorduras e açúcares, sendo estes vinculados normalmente aos alimentos industrializados. A consequência disso rapidamente se manifestou no aumento do sobrepeso/obesidade e na instalação de alterações fisiológicas e metabólicas, como a Síndrome Metabólica, que é representada por alterações na glicemia, nos lipídeos e na pressão arterial. Há evidências de ligação estreita entre estas alterações e os processos inflamatórios, que também podem estar associados ao estresse oxidativo. Estas condições levam à patogênese das alterações vasculares ou intensificam os processos metabólicos que acompanham a Síndrome Metabólica. O objetivo desta revisão foi comparar as inúmeras referências literárias que mostram correlação entre os componentes da Síndrome Metabólica e o aumento dos mediadores de inflamação. Para isso, utilizou-se Pubmed, Scopus, Lilacs e Scielo como base de dados, sendo que os artigos selecionados dataram principalmente dos últimos cinco anos.Palavras-chave: síndrome metabólica; arteriosclerose; inflamação.

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“…The onset of SSNHL is similar to that of myocardial infarction and cerebral stroke, both are majorly caused by atherosclerosis. Accumulating evidence indicates that atherosclerosis is a chronic vascular inflammatory disorder, and inflammatory reaction plays an essential role in the occurrence and progression of cardiovascular disease (Tuttolomondo et al 2012;Alie et al 2014;Liu et al 2016). Previous studies provided imaging evidence for the involvement of inflammation in the inner ear of SSNHL patients by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) (Berrettini et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss

Tian

Zhang

Yang

2018

Tohoku J. Exp. Med.

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Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation

Cited by 56 publications

References 100 publications

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Síndrome metabólica, aterosclerose e inflamação: tríade indissociável?

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss

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