High resolution magnetic resonance imaging in atherosclerotic mice treated with ezetimibe.
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.
Dietrich
Thore
T
Department of Internal Medicine, Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin, Germany.
Hucko
Thomas
T
Bourayou
Riad
R
Jahnke
Cosima
C
Paetsch
Ingo
I
Atrott
Kirstin
K
Stawowy
Philipp
P
Gräfe
Michael
M
Klein
Christoph
C
Schnackenburg
Bernhard
B
Fleck
Eckart
E
Graf
Kristof
K
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
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D001384:Azetidines; D002784:Cholesterol; D000069438:Ezetimibe