title: Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin.
abstract: BACKGROUND
  Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI).
  
  
  METHODS
  Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.
  
  
  RESULTS
  DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05).
  
  
  CONCLUSIONS
  After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.
authors.affiliation: General Hospital of Nanjing Military Region, Xuzhou, China; Department of Cardiology, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Qi
authors.affiliation: Institute of Cardiovascular Disease, Xuzhou Medical College, Xuzhou, China.
authors.forename: Liangrong
authors.initials: L
authors.lastname: Deng
authors.affiliation: General Hospital of Nanjing Military Region, Xuzhou, China; Institute of Cardiovascular Disease, Xuzhou Medical College, Xuzhou, China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Qingdui
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of magnetic resonance imaging, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of magnetic resonance imaging, Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular and Boimolecular Electronics, Southeast University, Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001012:Aorta, Abdominal; D050197:Atherosclerosis / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000628:therapy; D000069059:Atorvastatin / Q000494:pharmacology*; D023201:CD40 Ligand / Q000097:blood / Q000235:genetics; D002784:Cholesterol / Q000008:administration & dosage / Q000009:adverse effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000494:pharmacology*; D003911:Dextrans / Q000737:chemistry*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000209:etiology / Q000473:pathology / Q000628:therapy; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000628:therapy; D011817:Rabbits; D004113:Succimer / Q000737:chemistry; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D016159:Tumor Suppressor Protein p53; C097921:ferumoxtran-10; D023201:CD40 Ligand; D002784:Cholesterol; D000069059:Atorvastatin; D004113:Succimer; D020780:Matrix Metalloproteinase 9