DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2010-05-19 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Burtea Carmen , Laurent Sophie , Ballet S., Port M., Rousseaux O., Thirifays Coralie, Toubeau Gérard, Vander Elst Luce , Corot C., Muller Robert , "Development of a robust protocol for vulnerable plaque characterization by using two peptide-functionalized USPIO derivaties" in Contrast-enhanced biomedical imaging, 12th Bi-Annual Conference on Contrast Agents and Multimodal Molecular Imaging, Mons, Belgique, 2010

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Cardiologie et circulation (DI3321), Biologie moléculaire (DI3111), Chimie organique (DI1313), Chimie des colloïdes (DI1329), Imagerie médicale, radiologie, tomographie (DI3243)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)
Texte intégral :

Abstract(s) :

(Anglais) Purpose: Rupture of atherosclerotic plaque is the primary cause of sudden cardiac death mainly in the industrialized countries. The term “plaque rupture” defines a structural defect in the fibrous cap that separates a necrotic core from the lumen resulting in its exposure to the blood via a gap in the cap (Schwartz SM et al, Arterioscler Thromb Vasc Biol, 2007, 27, 705). In most patients, acute ischemic events are caused by the disruption of type IV and Va lipid-rich lesions, which are often not angiographically visible (Frank H, Am Heart J, 2001, 141, S45). ApoE-KO mouse model of atherosclerosis is characterized, in certain circumstances, by human-like plaque rupture events (Johnson JL & Jackson CL, Atherosclerosis, 2001, 154, 399). VCAM-1 and apoptotic cell-targeted peptides identified and validated during our previous work (Burtea C et al, J Med Chem, 2009, 52, 4725; Burtea C et al, Mol Pharm, 2009, 6, 1903) were now conjugated to USPIO (USPIO-R832 for VCAM-1 targeting; USPIO-R826 for apoptosis targeting) and assessed by MRI on ApoE-KO mice. The results were then correlated with several biomarkers of plaque vulnerability which were evaluated by immunohistochemistry. Materials and Methods: Female ApoE-KO mice injected with 100 µmol Fe/kg were imaged on a 4.7 T Bruker MRI at the level of abdominal aorta with RARE (TR/TE = 3000/20 ms, spatial resolution = 90 µm) and FLASH (TR/TE = 175/1.88 ms, flip angle = 90°, spatial resolution = 172 µm) imaging protocols. After MRI investigations, aortic samples were examined by histochemistry for the binding of contrast agent (Perl's staining protocol), the presence of collagen and thrombus (Masson’s trichrome staining), of angiogenic blood vessels (VCAM-1 and PECAM-1 staining), apoptotic cells (caspase-3), macrophages (Mac 1), cholesterol (Sudan IV), and smooth muscle cells (?-actin staining). The MR images and histological pictures were then analyzed with ImageJ software. Results: Both USPIO-R832 and USPIO-R826 produced a maximum negative contrast 30 min after administration (Fig. 1), being constant until the end of MRI studies (90 min). The plaque surface was measured on images and it was correlated to the level of plaque enhancement and to the histological observations. USPIO-R826 has mainly enhanced lipid-rich plaques, while this parameter did not seem to influence the binding of USPIO-R832 which enhanced fibrous plaques as well. Conclusion: Our VCAM-1 and apoptotic cell targeted USPIO derivatives seem to be highly promising tools for atherosclerosis imaging contributing to the detection of vulnerable plaques. They are able to attain their target in low doses and as fast as 30 min after administration.

Mots-clés :
  • (Anglais) atherosclerosis
  • (Anglais) apoptosis
  • (Anglais) phosphatidylserine
  • (Anglais) functionalized iron oxide nanoparticles
  • (Anglais) VCAM-1
  • (Anglais) vulnerable plaque
  • (Anglais) magnetic resonance imaging
  • (Anglais) inflammation