RT Journal Article
T1 Tropoelastin: A novel marker for plaque progression and instability
A1 Phinikaridou, Alkystis
A1 Lacerda, Sara
A1 Lavín Plaza, Begoña
A1 Andia, Marcelo E.
A1 Smith, Alberto
A1 Saha, Prakash
A1 Botnar, René
AB 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]
PB Wolters Kluwer Health
SN 1941-9651
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/98949
UL https://hdl.handle.net/20.500.14352/98949
LA eng
NO 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.
NO British Heart Foundation
NO Chilean Agency of Technology and Science
NO European Commission
NO Engineering & Physical Sciences Research Council (Reino Unido)
DS Docta Complutense
RD 8 abr 2025