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

Abstract

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 mm2), lesion size tended to increase in apoE-deficient to apoE-deficient grafts (0.2411 ± 0.0636 mm2; P =.06), whereas a significant reduction was seen in apoE–deficient to WT grafts (0.0214 ± 0.0049 mm2; 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. (J Vasc Surg 2001;34:541-7)