Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 24, Issue 9, Pages 1714-1719Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000139313.69015.1c
Keywords
atherosclerosis; imaging; lipoproteins; remodeling; transplantation
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Funding
- NHLBI NIH HHS [HL-61814, HL-07824, HL-70524] Funding Source: Medline
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Objective-We determined the effects of sustained normocholesterolemia on advanced mouse atherosclerosis and whether changes in plaque size and composition can be detected noninvasively by MRI. Methods and Results-Aortic arch segments containing advanced lesions from apolipoprotein E-deficient (apoE-/-) mice (total cholesterol 1281+/-97 mg/dL) were transplanted into syngeneic wild-type (WT; 111+/-11 mg/dL) or apoE-/- (702+/-74 mg/dL) recipient mice on chow diet. Mice underwent serial MRI at 3, 5, 7, and 9 weeks after transplantation. Compared with 3 weeks, correction of dyslipidemia in WT recipient mice resulted in a monotonic decrease (regression) in arterial wall volume, whereas in apoE-/- recipient mice, further plaque progression was noted (P<0.05). MRI and histological measurements were closely correlated (R=0.937). The lesional content of macrophages decreased >90% (P<0.001), and smooth muscle cells increased in the WT recipient mice. In vivo T-1-, T-2-, and proton density-weighted images of the mouse thoracic aorta differentiated intraplaque lipid and collagen. Conclusions-Plaque changes can be noninvasively monitored by serial in vivo MRI of a mouse regression model. Our ability to image the thoracic aorta and perform in vivo plaque characterization will further enhance atherosclerosis studies.
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