Extracellular Matrix-Specific Molecular MR Imaging Probes for the Assessment of Aortic Aneurysms

2018 ◽  
pp. 373-381
Author(s):  
Julia Brangsch ◽  
Carolin Reimann ◽  
Marcus R. Makowski
Keyword(s):  
Extracellular Matrix ◽  
Mr Imaging ◽  
Aortic Aneurysms ◽  
Imaging Probes

scholarly journals Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights

2021 ◽  
Vol 22 (5) ◽  
pp. 2685
Author(s):  
Lisa Adams ◽  
Julia Brangsch ◽  
Bernd Hamm ◽  
Marcus R. Makowski ◽  
Sarah Keller
Keyword(s):  
Extracellular Matrix ◽  
Molecular Imaging ◽  
Molecular Targets ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Type I ◽  
Target Tissue ◽  
Pharmacologic Treatment ◽  
Abdominal Aortic

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

scholarly journals Quantitative not qualitative histology differentiates aneurysmal from nondilated ascending aortas and reveals a net gain of medial components

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sameh Yousef ◽  
Nana Matsumoto ◽  
Issam Dabe ◽  
Makoto Mori ◽  
Alden B. Landry ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Quantitative Assessment ◽  
Cell Number ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Adaptive Responses ◽  
Cross Sectional ◽  
Thoracic Aortic Aneurysms ◽  
Medial Degeneration ◽  
The Media

AbstractMedial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

scholarly journals Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms

2017 ◽  
Vol 14 (130) ◽  
pp. 20161036 ◽  
Author(s):  
C. Bellini ◽  
M. R. Bersi ◽  
A. W. Caulk ◽  
J. Ferruzzi ◽  
D. M. Milewicz ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Structural Integrity ◽  
Ascending Aorta ◽  
Elastic Fibre ◽  
Cytoskeletal Proteins ◽  
Aortic Aneurysms ◽  
Genetic Mutations ◽  
Murine Models ◽  
Thoracic Aortic Aneurysms ◽  
Signalling Molecules

Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or rupture. In this paper, we compare the biaxial mechanical properties of the ascending aorta from 10 murine models: wild-type controls, acute elastase-treated, and eight models with genetic mutations affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal proteins, or intracellular signalling molecules. Collectively, our data for these diverse mouse models suggest that reduced mechanical functionality, as indicated by a decreased elastic energy storage capability or reduced distensibility, does not predispose to aneurysms. Rather, despite normal or lower than normal circumferential and axial wall stresses, it appears that intramural cells in the ascending aorta of mice prone to aneurysms are unable to maintain or restore the intrinsic circumferential material stiffness, which may render the wall biomechanically vulnerable to continued dilatation and possible rupture. This finding is consistent with an underlying dysfunctional mechanosensing or mechanoregulation of the extracellular matrix, which normally endows the wall with both appropriate compliance and sufficient strength.

Mural thrombi in abdominal aortic aneurysms: MR imaging characterization--useful before endovascular treatment?

Radiology ◽  
1995 ◽  
Vol 197 (1) ◽  
pp. 135-139 ◽  
Author(s):  
M Castrucci ◽  
R Mellone ◽  
A Vanzulli ◽  
A De Gaspari ◽  
R Castellano ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Endovascular Treatment ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Imaging Characterization

scholarly journals MATRIX METALLOPROTEINASES AND EXTRACELLULAR MATRIX PROTEINS IN PATIENTS WITH ASCENDING AORTIC ANEURYSMS: PP.31.245

2010 ◽  
Vol 28 ◽  
pp. e522-e523
Author(s):  
O Irtyuga ◽  
D Gamazin ◽  
I Voronkina ◽  
N Tsoyi ◽  
V Uspensky ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Extracellular Matrix Proteins ◽  
Aortic Aneurysms ◽  
Matrix Proteins

Responsive MR-imaging probes for N-methyl-d-aspartate receptors and direct visualisation of the cell-surface receptors by optical microscopy

2013 ◽  
Vol 4 (8) ◽  
pp. 3148 ◽  
Author(s):  
Neil Sim ◽  
Sven Gottschalk ◽  
Robert Pal ◽  
Jörn Engelmann ◽  
David Parker ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Cell Surface ◽  
Optical Microscopy ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Imaging Probes

Abstract 496: Extracellular Matrix Secretion by Vascular Smooth Muscle Cells: Role of MiR-195 and MiR-29b

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anna Zampetaki ◽  
Xiaoke Yin ◽  
Ursula Mayr ◽  
Renata Gomes ◽  
Sarah Langley ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Vascular Smcs

Rationale: Extracellular matrix (ECM) remodeling is a key function of vascular smooth muscle cells (SMCs). MicroRNAs (miRNAs), in particular the miR-29 family and miR-195, have been implicated in the control of ECM secretion. Objective: To perform a proteomics comparison of miRNA effects on ECM production by vascular SMCs. Methods and Results: Murine SMCs were transfected with miRNA mimics and antimiRs of miR-29b and miR-195, and their conditioned medium was analyzed by mass spectrometry. Both miRNAs targeted a cadre of ECM proteins, including proteoglycans, collagens, proteases, elastin and proteins associated with elastic microfibrils, albeit miR-29 showed a stronger effect. The proteomics findings were subsequently validated at the transcription level using quantitative polymerase chain reaction. Similar to miR-29, in vivo inhibition of miR-195 by intraperitoneal injection of cholesterol bound antagomiRs led to significant alterations of elastin expression in murine aortas. Since elastin degradation is a key event in aortic aneurysm formation, we investigated miR-195 expression in patients. In human aortic aneurysmal tissue, miR-195 expression was reduced compared to non-aneurysmal tissue. In plasma, a comparison between male patients with abdominal aortic aneurysms and controls matched for diabetes and hypertension returned a panel of five highly correlated miRNAs: miR-195, miR-125b, miR-148a, miR-20a and miR-340 showed significant inverse associations with the presence of abdominal aortic aneurysms and aortic diameter, with miR-195 dominating in terms of association strength. Conclusions: Using proteomic analysis, we compared the effect of miR-29 and miR-195 on ECM secretion by vascular SMCs and identified novel miRNA targets. Findings in patients support an important role for miR-195 in vascular remodeling as evidenced by reduced miR-195 expression in human aneurysmal tissue and an inverse correlation between plasma miR-195 levels and aortic diameter.

scholarly journals 2464 Sexual dimorphism in a mouse model of syndromic thoracic aortic aneurysm

2018 ◽  
Vol 2 (S1) ◽  
pp. 27-27
Author(s):  
Zheying Chen ◽  
Alan Daugherty ◽  
Mary Sheppard
Keyword(s):  
Extracellular Matrix ◽  
Sexual Dimorphism ◽  
Mouse Model ◽  
Aortic Aneurysms ◽  
Pcr Analysis ◽  
Wild Type ◽  
Aortic Dilation ◽  
Male And Female ◽  
Thoracic Aortic Aneurysms ◽  
Male Sex

OBJECTIVES/SPECIFIC AIMS: Pre-clinical and clinical observations have noted that increased aortic dilation is associated with male sex. Using an experimental model of severe, syndromic thoracic aortic aneurysms, we quantify aortic dilation and elastin stability in male Versus female mice. METHODS/STUDY POPULATION: Ascending aortas from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. At termination, aortas were harvested for RT-PCR analysis of extracellular matrix genes. Aortas were serially sectioned and elastin fragmentation was imaged by auto-fluorescence. RESULTS/ANTICIPATED RESULTS: At 12 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice were significantly different (2.24±0.43 vs. 1.57±0.22 mm; p=0.002), while there were no significant differences between sexes of wild type littermates (1.29±0.13 vs. 1.23±0.08 mm; p=0.71). Male sex was associated with increased elastin but not fibrillin-1 mRNA expression. Ascending aortas from male and female FBN1mgR/mgR mice significantly differed in the degree of elastin fragmentation (2.76 vs. 1.85 breaks/ 100 µm aorta; p=0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Sexual dimorphism of thoracic aortic dilation observed in human TAA patients was recapitulated in the fibirllin-1 hypomorphic mouse model of syndromic thoracic aortic aneurysms. Differences in this mouse model could be explained by the differential expression of extracellular matrix genes.

scholarly journals Extracellular matrix in ascending aortic aneurysms and dissections – What we learn from decellularization and scanning electron microscopy

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0213794 ◽  
Author(s):  
Teresa Mimler ◽  
Clemens Nebert ◽  
Eva Eichmair ◽  
Birgitta Winter ◽  
Thomas Aschacher ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Extracellular Matrix ◽  
Aortic Aneurysms ◽  
Scanning Electron
Sign in / Sign up

Export Citation Format

Share Document