Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model.
OBJECTIVE
Regression of atherosclerotic lesions is an important goal. No extensive experimental evidence shows that it can be achieved for advanced lesions. To study this, we developed a model to maintain a long-term change in the plasma lipoprotein environment of advanced arterial lesions of hyperlipidemic (apolipoprotein E [apoE]-deficient) mice.


METHODS
The apoE-deficient mice (plasma total cholesterol of 1334 +/- 219 [+/- SEM] mg/dL) on a typical Western diet for 38 weeks had advanced atherosclerotic lesions (ie, beyond the macrophage foam cell stage) throughout the arterial tree. Lesion-containing thoracic aortas were transplanted (replacing a segment of abdominal aorta) into either apoE-deficient or wild-type (WT) (total cholesterol of 86 +/- 10 mg/dL) recipients. Grafts were harvested after 9 weeks.


RESULTS
Compared with pretransplant lesions (area = 0.0892 +/- 0.0179 mm(2)), lesion size tended to increase in apoE-deficient to apoE-deficient grafts (0.2411 +/- 0.0636 mm(2); P =.06), whereas a significant reduction was seen in apoE-deficient to WT grafts (0.0214 +/- 0.0049 mm(2); P <.001). Also, foam cells were absent in apoE-deficient to WT grafts, but abundant in pretransplant lesions and apoE-deficient to apoE-deficient grafts. Grafts were evaluated noninvasively in vivo with magnetic resonance imaging, and wall thickening was detected in the apoE-deficient to apoE-deficient group.


CONCLUSIONS
Nearly complete regression of advanced atherosclerotic lesions can be achieved with sustained normalization of the plasma lipoprotein profile. Syngeneic arterial transplantation in mice is a novel and valuable model system for atherosclerosis research; and magnetic resonance imaging can detect differences in characteristics in lesions undergoing regression.
Reis
E D
ED
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Li
J
J
Fayad
Z A
ZA
Rong
J X
JX
Hansoty
D
D
Aguinaldo
J G
JG
Fallon
J T
JT
Fisher
E A
EA
D000818:Animals; D001011:Aorta / Q000637:transplantation; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology* / Q000601:surgery*; D006949:Hyperlipidemias / Q000150:complications; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1