{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:48:57Z","timestamp":1790711337742,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Imaging"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Elastolysis and ineffective elastogenesis favor the accumulation of tropoelastin, rather than cross-linked elastin, in atherosclerotic plaques. We developed gadolinium-labeled tropoelastin-specific magnetic resonance contrast agents for tropoelastin imaging in animal models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              Two peptides, VVGSPSAQDEASPLS and YPDHVQYTHY, were selected to target tropoelastin. In vitro binding, relaxivity, and biodistribution experiments enabled characterization of the probes and selecting the best candidate for in vivo magnetic resonance imaging. Magnetic resonance imaging was performed in atherosclerotic apolipoprotein E\u2013deficient mice and New Zealand white rabbits with stable and rupture-prone plaques using a gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent. In addition, human carotid endarterectomy specimens were imaged ex vivo. The VVGSPSAQDEASPLS-based probe discriminated between tropoelastin and cross-linked elastin (64%\u00b17% versus 1%\u00b12%;\n              <jats:italic>P<\/jats:italic>\n              =0.001), had high in vitro relaxivity in solution (r\n              <jats:sub>1-free<\/jats:sub>\n              =11.7\u00b10.6 [mmol\/L]\n              <jats:sup>\u22121<\/jats:sup>\n              s\n              <jats:sup>\u22121<\/jats:sup>\n              , r\n              <jats:sub>1-bound to tropoelastin<\/jats:sub>\n              =44\u00b11 [mmol\/L]\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>1<\/jats:sup>\n              s\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>1<\/jats:sup>\n              ), and favorable pharmacokinetics. In vivo mice vascular enhancement (4 weeks=0.13\u00b10.007 mm\n              <jats:sup>2<\/jats:sup>\n              , 8 weeks=0.22\u00b10.01 mm\n              <jats:sup>2<\/jats:sup>\n              , 12 weeks=0.33\u00b10.01 mm\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and R\n              <jats:sub>1<\/jats:sub>\n              relaxation rate (4 weeks=[0.90\u00b10.01]\/s, 8 weeks=[1.40\u00b10.03]\/s, 12 weeks=[1.87\u00b10.04]\/s;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) increased with atherosclerosis progression after gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent injection. Conversely, statin-treated (0.13\u00b10.01 mm\n              <jats:sup>2<\/jats:sup>\n              ; R\n              <jats:sub>1<\/jats:sub>\n              =[1.37\u00b10.03]\/s) and control (0.10\u00b10.005 mm\n              <jats:sup>2<\/jats:sup>\n              ; R\n              <jats:sub>1<\/jats:sub>\n              =[0.87\u00b10.05]\/s) mice showed less enhancement. Rupture-prone rabbit plaques had higher R\n              <jats:sub>1<\/jats:sub>\n              relaxation rate compared with stale plaques (R\n              <jats:sub>1<\/jats:sub>\n              =[2.26\u00b10.1]\/s versus R\n              <jats:sub>1<\/jats:sub>\n              =[1.43\u00b10.02]\/s;\n              <jats:italic>P<\/jats:italic>\n              =0.001) after administration of the gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent that allowed detection of rupture-prone plaques with high sensitivity (84.4%) and specificity (92.3%). Increased vascular R\n              <jats:sub>1<\/jats:sub>\n              relaxation rate was observed in carotid endarterectomy plaques after soaking (R\n              <jats:sub>1pre<\/jats:sub>\n              =[1.1\u00b10.26]\/s versus R\n              <jats:sub>1post<\/jats:sub>\n              =[3.0\u00b10.1]\/s;\n              <jats:italic>P<\/jats:italic>\n              =0.01). Ex vivo analyses confirmed the magnetic resonance imaging findings and showed uptake of the contrast agent to be specific for tropoelastin.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Magnetic resonance imaging of tropoelastin provides a novel biomarker for atherosclerotic plaque progression and instability.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circimaging.117.007303","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T19:50:22Z","timestamp":1536954622000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Tropoelastin"],"prefix":"10.1161","volume":"11","author":[{"given":"Alkystis","family":"Phinikaridou","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering and Imaging Sciences (A.P., S.L., B.L., M.E.A., R.M.B.)"},{"name":"BHF Centre of Excellence, Cardiovascular Division (A.P., S.L., B.L., R.M.B.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lacerda","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Imaging Sciences (A.P., S.L., B.L., M.E.A., R.M.B.)"},{"name":"BHF Centre of Excellence, Cardiovascular Division (A.P., S.L., B.L., R.M.B.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Lavin","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Imaging Sciences (A.P., S.L., B.L., M.E.A., R.M.B.)"},{"name":"BHF Centre of Excellence, Cardiovascular Division (A.P., S.L., B.L., R.M.B.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo E.","family":"Andia","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Imaging Sciences (A.P., S.L., B.L., M.E.A., R.M.B.)"},{"name":"Radiology Department, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago (M.E.A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Smith","sequence":"additional","affiliation":[{"name":"Academic Department of Vascular Surgery, Cardiovascular Division (A.S., P.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Saha","sequence":"additional","affiliation":[{"name":"Academic Department of Vascular Surgery, Cardiovascular Division (A.S., P.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 M.","family":"Botnar","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Imaging Sciences (A.P., S.L., B.L., M.E.A., R.M.B.)"},{"name":"BHF Centre of Excellence, Cardiovascular Division (A.P., S.L., B.L., R.M.B.)"},{"name":"Wellcome Trust and EPSRC Medical Engineering Center (R.M.B.), King\u2019s College London, United Kingdom"},{"name":"Pontificia Universidad Cat\u00f3lica de Chile, Escuela de Ingenier\u00eda, Santiago, Chile (R.M.B)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.155911"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/493S2a"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00171-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2012.12.004"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(03)00065-3"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000064372.78561.A5"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(65)90015-8"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.12.2566"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2011.10.006"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.03.017"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.126.2.563"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22361"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22817"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)46947-5"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(80)90023-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.10.267"},{"key":"e_1_3_4_18_2","first-page":"617","article-title":"Analysis of elastin cross-linking and the connective tissue matrix of abdominal aortic aneurysms.","volume":"115","author":"Gandhi RH","year":"1994","unstructured":"Gandhi, RH, Irizarry, E, Cantor, JO, Keller, S, Nackman, GB, Halpern, VJ, Newman, KM, Tilson, MD. 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