Tropoelastin: A novel marker for plaque progression and instability

Circulation. Cardiovascular Imaging
Alkystis PhinikaridouRene M Botnar

Abstract

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. 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<0.001) increased with atherosclerosis prog...Continue Reading

References

Apr 14, 1989·Biochemical and Biophysical Research Communications·D B BadeschK R Stenmark
Oct 1, 1965·Experimental and Molecular Pathology·M D HaustJ U Balis
Oct 1, 1980·The Journal of Clinical Investigation·R M SeniorR P Mecham
Dec 23, 1998·Atherosclerosis·L RobertB Jacotot
Sep 17, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Cristina RodríguezLina Badimon
Oct 4, 2002·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Nafiseh NiliMichelle P Bendeck
Mar 5, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Alexandra KrettekPeter Libby
Jul 3, 2003·Trends in Cardiovascular Medicine·Benjamin S BrookeDean Y Li
Jan 14, 2004·Journal of Atherosclerosis and Thrombosis·Shogo Katsuda, Toshiyuki Kaji
Jun 14, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Camille BrasseletAntoine Lafont
Feb 14, 2006·The Journal of Clinical Investigation·A McGarry HoughtonSteven D Shapiro
Mar 31, 2006·Journal of Medical Genetics·P N RobinsonM Godfrey
Sep 26, 2007·Angewandte Chemie·Peter CaravanZhaoda Zhang
Apr 9, 2008·Journal of the American Chemical Society·Kirsten Overoye-ChanPeter Caravan
May 13, 2008·The International Journal of Biochemistry & Cell Biology·Steven G Wise, Anthony S Weiss
May 13, 2008·Cardiovascular Research·Cristina RodríguezLina Badimon
Jan 15, 2009·Journal of Lipid Research·Alkystis PhinikaridouJames A Hamilton
May 2, 2009·Cardiovascular Research·Cristina RodríguezLina Badimon
Mar 3, 2010·Circulation. Cardiovascular Imaging·Alkystis PhinikaridouJames A Hamilton
Mar 8, 2011·Circulation. Cardiovascular Imaging·Christian von BaryRené Botnar
Oct 28, 2011·Biochimie·Andrea HeinzChristian E H Schmelzer
Dec 15, 2012·Circulation·Stephen SidneyUNKNOWN National Forum for Heart Disease and Stroke Prevention
Apr 9, 2013·Trends in Cardiovascular Medicine·Pascal MauriceLaurent Duca
Dec 24, 2013·Circulation. Cardiovascular Imaging·Moritz WildgruberRené M Botnar
May 30, 2014·Circulation. Cardiovascular Imaging·René M BotnarMarcus R Makowski

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Citations

Mar 4, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Mani SalarianJenny J Yang
Jun 13, 2020·Critical Reviews in Biochemistry and Molecular Biology·Andrea Heinz
Oct 26, 2018·Circulation. Cardiovascular Imaging·Raphaël Duivenvoorden, Willem J M Mulder
Jul 10, 2019·Current Cardiovascular Imaging Reports·Begoña Lavin PlazaRene M Botnar
Jul 10, 2019·Cardiovascular Research·Begoña LavinAlkystis Phinikaridou
Sep 8, 2019·Matrix Biology : Journal of the International Society for Matrix Biology·Wassim FhayliGilles Faury
Mar 16, 2021·Frontiers in Bioengineering and Biotechnology·Jazmin OzsvarAnthony S Weiss
Jul 29, 2021·Current Opinion in Lipidology·Chrysostomi GialeliIsabel Gonçalves

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