RT Journal Article
T1 Tropoelastin: an in vivo imaging marker of dysfunctional matrix turnover during abdominal aortic dilation
A1 Lavín Plaza, Begoña
A1 Lacerda, Sara
A1 Andia, Marcelo
A1 Lorrio, Silvia
A1 Bakewell, Robert
A1 Smith, Alberto
A1 Rashid, Imran
A1 Botnar, René M.
A1 Phinikaridou, Alkystis
AB AimsDysfunctional 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.Methods and resultsWe 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.ConclusionTropoelastin 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.
PB Oxford University Press
SN 1755-3245
YR 2019
FD 2019-04-01
LK https://hdl.handle.net/20.500.14352/97797
UL https://hdl.handle.net/20.500.14352/97797
LA eng
NO Begoña Lavin, Sara Lacerda, Marcelo E Andia, Silvia Lorrio, Robert Bakewell, Alberto Smith, Imran Rashid, René M Botnar, Alkystis Phinikaridou, Tropoelastin: an in vivo imaging marker of dysfunctional matrix turnover during abdominal aortic dilation, Cardiovascular Research, Volume 116, Issue 5, 1 April 2020, Pages 995–1005, https://doi.org/10.1093/cvr/cvz178
NO British Heart Foundation
NO Chilean Agency of Technology and Science
NO European Commission
DS Docta Complutense
RD 10 abr 2025