Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model

J Vasc Surg. 2001 Sep;34(3):541-7. doi: 10.1067/mva.2001.115963.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / transplantation
  • Apolipoproteins E / deficiency*
  • Arteriosclerosis / etiology
  • Arteriosclerosis / pathology*
  • Arteriosclerosis / surgery*
  • Hyperlipidemias / complications
  • Intercellular Adhesion Molecule-1 / analysis
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal*
  • Vascular Cell Adhesion Molecule-1 / analysis


  • Apolipoproteins E
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1