PMID- 31282949 OWN - NLM STAT- MEDLINE DCOM- 20201019 LR - 20221207 IS - 1755-3245 (Electronic) IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 116 IP - 5 DP - 2020 Apr 1 TI - Tropoelastin: an in vivo imaging marker of dysfunctional matrix turnover during abdominal aortic dilation. PG - 995-1005 LID - 10.1093/cvr/cvz178 [doi] AB - AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Lavin, Begona AU - Lavin B AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. AD - Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK. FAU - Lacerda, Sara AU - Lacerda S AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. AD - Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK. AD - Centre de Biophysique Moleculaire, CNRS, Orleans, France. FAU - Andia, Marcelo E AU - Andia ME AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. AD - Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Lorrio, Silvia AU - Lorrio S AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. AD - Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK. FAU - Bakewell, Robert AU - Bakewell R AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. FAU - Smith, Alberto AU - Smith A AD - Cardiovascular Division, Academic Department of Vascular Surgery, King's College London, London, UK. FAU - Rashid, Imran AU - Rashid I AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. FAU - Botnar, Rene M AU - Botnar RM AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. AD - Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK. AD - Wellcome Trust and EPSRC Medical Engineering Center, King's College London, London, UK. AD - Pontificia Universidad Catolica de Chile, Escuela de Ingenieria, Santiago, Chile. FAU - Phinikaridou, Alkystis AU - Phinikaridou A AD - School of Biomedical Engineering and Imaging Sciences, Department of Biomedical Engineering, King's College London, 3rd Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, UK. AD - Cardiovascular Division, BHF Centre of Excellence, King's College London, London, UK. LA - eng GR - RG/12/1/29262/BHF_/British Heart Foundation/United Kingdom GR - 203148/WT_/Wellcome Trust/United Kingdom GR - DH_/Department of Health/United Kingdom GR - RE/08/03/BHF_/British Heart Foundation/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Biomarkers) RN - 0 (Contrast Media) RN - 0 (Tropoelastin) RN - 11128-99-7 (Angiotensin II) SB - IM MH - Aortic Dissection/chemically induced/*diagnostic imaging/metabolism/pathology MH - Angiotensin II MH - Animals MH - Aorta, Abdominal/*diagnostic imaging/metabolism/pathology MH - Aortic Aneurysm, Abdominal/chemically induced/*diagnostic imaging/metabolism/pathology MH - Biomarkers/metabolism MH - Contrast Media/*administration & dosage/metabolism MH - Dilatation, Pathologic MH - Disease Models, Animal MH - Disease Progression MH - Extracellular Matrix/*metabolism/pathology MH - Humans MH - *Magnetic Resonance Imaging MH - Mice, Knockout, ApoE MH - Predictive Value of Tests MH - Proof of Concept Study MH - Time Factors MH - Tropoelastin/*metabolism MH - Up-Regulation MH - *Vascular Remodeling PMC - PMC7104357 MID - EMS84567 OTO - NOTNLM OT - Aneurysm OT - Dissections OT - Elastin OT - MRI OT - Matrix turnover OT - Molecular imaging OT - Tropoelastin COIS- Conflict of interest: none declared. EDAT- 2019/07/10 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/04/01 CRDT- 2019/07/09 06:00 PHST- 2019/06/06 00:00 [received] PHST- 2019/07/05 00:00 [accepted] PHST- 2019/07/10 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2019/07/09 06:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - 5529672 [pii] AID - 10.1093/cvr/cvz178 [doi] PST - ppublish SO - Cardiovasc Res. 2020 Apr 1;116(5):995-1005. doi: 10.1093/cvr/cvz178.