Tropoelastin: an in vivo imaging marker of dysfunctional matrix turnover during abdominal aortic dilation.
Aortic Dissection
/ chemically induced
Angiotensin II
Animals
Aorta, Abdominal
/ diagnostic imaging
Aortic Aneurysm, Abdominal
/ chemically induced
Biomarkers
/ metabolism
Contrast Media
/ administration & dosage
Dilatation, Pathologic
Disease Models, Animal
Disease Progression
Extracellular Matrix
/ metabolism
Humans
Magnetic Resonance Imaging
Mice, Knockout, ApoE
Predictive Value of Tests
Proof of Concept Study
Time Factors
Tropoelastin
/ metabolism
Up-Regulation
Vascular Remodeling
Aneurysm
Dissections
Elastin
MRI
Matrix turnover
Molecular imaging
Tropoelastin
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
06
06
2019
accepted:
05
07
2019
pubmed:
10
7
2019
medline:
21
10
2020
entrez:
9
7
2019
Statut:
ppublish
Résumé
Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulation of monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific magnetic resonance contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlates with aortic expansion in a murine model. The binding of Gd-TESMA to excised human AAA was also assessed. We utilized the angiotensin II (Ang II)-infused apolipoprotein E gene knockout (ApoE-/-) murine model of aortic dilation and performed in vivo imaging of tropoelastin by administering Gd-TESMA followed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) and T1 mapping at 3 T, with subsequent ex vivo validation. In a cross-sectional study (n = 66; control = 11, infused = 55) we found that Gd-TESMA enhanced MRI was elevated and confined to dilated aortic segments (control: LGE=0.13 ± 0.04 mm2, control R1= 1.1 ± 0.05 s-1 vs. dilated LGE =1.0 ± 0.4 mm2, dilated R1 =2.4 ± 0.9 s-1) and was greater in segments with medium (8.0 ± 3.8 mm3) and large (10.4 ± 4.1 mm3) compared to small (3.6 ± 2.1 mm3) vessel volume. Furthermore, a proof-of-principle longitudinal study (n = 19) using Gd-TESMA enhanced MRI demonstrated a greater proportion of tropoelastin: elastin expression in dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Treatment with pravastatin and aspirin (n = 10) did not reduce tropoelastin turnover (0.87 ± 0.3 mm2 vs. 1.0 ± 0.44 mm2) or aortic dilation (4.86 ± 2.44 mm3 vs. 4.0 ± 3.6 mm3). Importantly, Gd-TESMA-enhanced MRI identified accumulation of tropoelastin in excised human aneurysmal tissue (n = 4), which was confirmed histologically. Tropoelastin MRI identifies dysfunctional matrix remodelling that is specifically expressed in regions of aortic aneurysm or dissection and correlates with the development and rate of aortic expansion. Thus, it may provide an additive imaging marker to the serial assessment of luminal diameter for surveillance of patients at risk of or with established aortopathy.
Identifiants
pubmed: 31282949
pii: 5529672
doi: 10.1093/cvr/cvz178
pmc: PMC7104357
mid: EMS84567
doi:
Substances chimiques
Biomarkers
0
Contrast Media
0
Tropoelastin
0
Angiotensin II
11128-99-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
995-1005Subventions
Organisme : British Heart Foundation
ID : RG/12/1/29262
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203148
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/08/03
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
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