Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture

Adams, Lisa C.; Brangsch, Julia; Reimann, Carolin; Kaufmann, Jan; Buchholz, Rebecca; Kärst, Uwe; Botnar, René M.; Hamm, Bernd; Makowski, Marcus R.

doi:10.1038/s41598-020-71817-x

Cited by 15 publications

(12 citation statements)

References 38 publications

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“…Ferumoxytol is not only used in imaging techniques for tumor diseases but may also have applications in cardiovascular diseases [ 21 , 22 , 44 ] and the central nervous system [ 15 ]. Different studies have investigated the molecular properties of cardiovascular disease with a combined approach using iron-oxide nanoparticles and a gadolinium-based contrast agent [ 21 , 22 , 44 ]. A limitation that needs to be considered regarding ferumoxytol is that it is not prostate tumor specific or even tumor specific.…”

Section: Discussionmentioning

confidence: 99%

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

Kader

Kaufmann

Mangarova

et al. 2022

Cancers

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Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm3 and 1000 mm3. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm3 than for 1000 mm3. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm3 tumors had 1.5% iron content (n = 14; σ = 1.1), while the 1000 mm3 tumors contained only 0.4% iron (n = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R2 = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R2 = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.

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Section: Discussionmentioning

confidence: 99%

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

Kader

Kaufmann

Mangarova

et al. 2022

Cancers

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“…It emphasized the role of collagen components in maintaining aneurysm structure integrity and prompted a great possibility of taking it as a prediction biomarker for future study. Future collagen‐specific MRI may aid the evaluation of BBA rupture prediction 26 …”

Section: Discussionmentioning

confidence: 99%

Reduced M2 macrophages and adventitia collagen dampen the structural integrity of blood blister–like aneurysms and induce preoperative rerupture

Wen

Chen

et al. 2021

Cell Proliferation

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Objective Blood blister–like aneurysms (BBAs) are extremely rare aneurysms. They are predisposed to preoperative rerupture with a high case‐fatality rate. Here, we attempt to interrogate the distinct clinicopathology and the histological basis underlying its clinical rerupture. Methods Three middle meningeal arteries, 11 BBA (5 reruptured, 6 non‐rerupture) and 19 saccular aneurysm samples were obtained for histopathological investigation. Three reruptured BBAs, 3 non‐reruptured BBAs and 6 saccular (3 ruptured, 3 unruptured) aneurysms were obtained for quantitative flow cytometry analysis. Results Compared with true saccular aneurysms, the BBA aneurysm wall lacks arterial stroma cells including CD31+ endothelial cells and α‐SMA + smooth muscle cells. Only fibroblasts and adventitial collagen were observed in the BBA aneurysm wall. Meanwhile, BBAs were enriched with infiltrated inflammatory cells, especially polarized macrophages. Based on the rerupture status, those reruptured BBAs showed drastically reduced fibroblasts and adventitia collagen. Moreover, M2‐polarized macrophages were observed dominant in BBAs and exhibit repairing cellular functions based on their interplays with arterial fibroblasts. Reduced M2 macrophages and arterial tissue repairing modulation may be responsible for the decreasing collagen synthesis and fibrosis repairment, which potentially dampens the aneurysm integrity and induces BBA aneurysm reruputre. Conclusions BBAs poses histopathological features of occult pseudoaneurysms or dissecting aneurysms. Reduced M2 macrophages and adventitia collagen may dampen the structural integrity of BBAs and induce preoperative rerupture.

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“…It is reported that an increased replacement of ECM collagen without adequately matched collagen deposition is a critical factor for AAA rupture in the dissection ( Jana et al, 2019 ; Adams et al, 2020 ). There are various underlying mechanisms implicated in the pathogenesis of AAA, including ECM degradation.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA RBM33 contributes to extracellular matrix degradation via miR-4268/EPHB2 axis in abdominal aortic aneurysm

Wang¹,

Yuan²,

Zhao³

et al. 2021

PeerJ

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Background Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. Extracellular matrix (ECM) degradation is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed circular RNAs (DEcircRNAs) involved in ECM degradation of AAA. Methods Transcriptome sequencing was used to analyze the DEcircRNAs between the AAA tissues and normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNAs in vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II) was employed to explore its effect on ECM degradation of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to evaluate the regulatory mechanism of circRNA. Results We identified 65 DEcircRNAs in AAA tissues compared with normal abdominal aortic tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and Ang II-induced VSMCs compared with control samples. Overexpression of circRBM33 increased the expression of ECM-related molecule matrix metalloproteinase-2 and reduced the tissue inhibitor of matrix metalloproteinases-1 expression. Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. Overexpression of circRBM33 induced the expression of EPH receptor B2 (EPHB2), and this effect was countered by miR-4268 mimics. Conclusions Overall, our data suggest that circRBM33 might be involved in AAA progression by regulating ECM degradation via the miR-4268/EPHB2 axis.

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Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture

Cited by 15 publications

References 38 publications

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

Reduced M2 macrophages and adventitia collagen dampen the structural integrity of blood blister–like aneurysms and induce preoperative rerupture

Circular RNA RBM33 contributes to extracellular matrix degradation via miR-4268/EPHB2 axis in abdominal aortic aneurysm

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