title: High resolution magnetic resonance imaging in atherosclerotic mice treated with ezetimibe.
abstract: High field magnetic resonance imaging (MRI) was performed to investigate the long-term effect of ezetimibe (eze), a cholesterol resorption blocker, on atherosclerotic lesion formation in the thoracic aorta of apolipoprotein E-deficient mice (apoE ( -/- )) in comparison to wild type mice (WT). Fifteen-month-old apoE ( -/- ) (Western type diet), apoE ( -/-eze ) (Western type diet with eze) which received eze (5 mc/kg/day) continuously, and age-matched WT (normal chow) were studied using contrast-enhanced 3D turbo-spin-echo sequences (RARE factor 2) on a 7 Tesla scanner. Vessel parameters were analyzed in the aortic root (AR) and aortic arch (AA) and compared to those found in histology. Plasma cholesterol levels were reduced at 15 months by 71% (P < 0.01) in apoE ( -/-eze ) compared to apoE ( -/- ). Vessel wall thickness was increased in the AR and AA in apoE ( -/- ) by 189.1 and 147.2%, respectively compared to WT. ApoE ( -/-eze ) showed reduced wall thickness in the AR (127.4%) and AA (102.8%, both P < 0.05 vs. apoE ( -/- )). A significant increase in total aortic vessel area was determined in the AR and AA in apoE ( -/- ) by 134.7 and 118.3%, respectively, compared to WT. This effect was inhibited in apoE ( -/-eze ) (AR: 126.7%, AA: 86.4%, both P < 0.05). Histological analysis confirmed the effect of eze observed by MRI and demonstrated a significant correlation between the two techniques (P < 0.001). MRI demonstrates that ezetimibe significantly reduces atherosclerotic disease in apoE ( -/- ). MRI is therefore a useful technique to perform in vivo interventional studies in experimental atherosclerosis.
authors: Department of Internal Medicine, Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin, Germany.
authors: Thore
authors: T
authors: Dietrich
authors: Thomas
authors: T
authors: Hucko
authors: Riad
authors: R
authors: Bourayou
authors: Cosima
authors: C
authors: Jahnke
authors: Ingo
authors: I
authors: Paetsch
authors: Kirstin
authors: K
authors: Atrott
authors: Philipp
authors: P
authors: Stawowy
authors: Michael
authors: M
authors: Gräfe
authors: Christoph
authors: C
authors: Klein
authors: Bernhard
authors: B
authors: Schnackenburg
authors: Eckart
authors: E
authors: Fleck
authors: Kristof
authors: K
authors: Graf
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D001384:Azetidines / Q000494:pharmacology*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D000069438:Ezetimibe; D018810:Magnetic Resonance Angiography; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D001384:Azetidines; D002784:Cholesterol; D000069438:Ezetimibe