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oai:docta.ucm.es:20.500.14352/989492024-08-19T23:54:45Zcom_20.500.14352_14col_20.500.14352_15

Phinikaridou, Alkystis Lacerda, Sara Lavín Plaza, Begoña Andia, Marcelo E. Smith, Alberto Saha, Prakash Botnar, René 2024-02-05T12:49:57Z 2024-02-05T12:49:57Z 2018 Phinikaridou, Alkystis, et al. «Tropoelastin: A Novel Marker for Plaque Progression and Instability». Circulation: Cardiovascular Imaging, vol. 11, n.o 8, agosto de 2018, p. e007303. https://doi.org/10.1161/CIRCIMAGING.117.007303. 1941-9651 10.1161/circimaging.117.007303 https://hdl.handle.net/20.500.14352/98949 1942-0080 https://doi.org/10.1161/CIRCIMAGING.117.007303 Background: 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 (Gd-TESMAs) for tropoelastin imaging in animal models. Methods and Results: 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 MRI. MRI was performed in atherosclerotic apolipoprotein E-deficient (ApoE-/-) mice and New Zealand white rabbits with stable and rupture-prone plaques using Gd-TESMA. Additionally, human carotid endarterectomy specimens were imaged ex vivo. The VVGSPSAQDEASPLS-based probe discriminated between tropoelastin and cross-linked elastin (64±7% vs 1±2%, P=0.001), had high in vitro relaxivity in solution (r1-free=11.7±0.6mM-1s-1, r1-bound to tropoelastin = 44±1mM-1s-1) and favorable pharmacokinetics. In vivo mice vascular enhancement (4wks=0.13±0.007mm2, 8wks=0.22±0.01mm2, 12wks=0.33±0.01mm2, P<0.001) and R1 relaxation rate (4wks=0.90±0.01 s-1, 8wks=1.40±0.03 s-1, 12wks=1.87±0.04s-1, P[removed] eng open access Tropoelastin: A novel marker for plaque progression and instability journal article