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 e xtensive experimental evidence shows that it can be achieved for advanced l esions. To study this, we developed a model to maintain a long-term change in the plasma lipoprotein environment of advanced arterial lesions of hyper lipidemic (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 athero sclerotic lesions (ie, beyond the macrophage foam cell stage) throughout th e arterial tree. Lesion-containing thoracic aortas were transplanted (repla cing a segment of abdominal aorta) into either apoE-deficient or wild-type (WT) (total cholesterol of 86 +/- 10 mg/dL) recipients. Grafts were harvest ed 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 graf ts (0.2411 +/- 0.0636 mm(2); P = .06), whereas a significant reduction was seen in apoE-dcficient to WT grafts (0.0214 +/- 0.0049 mm(2); p < .001). Al so, foam cells were absent in apoE-deficient to WT grafts, but abundant in pretransplant lesions and apoE-deficient to apoE-deficient grafts. Grafts w ere evaluated non-invasively in vivo with magnetic resonance imaging, and w all 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 pro file. Syngeneic arterial transplantation in mice is a novel and valuable mo del system for atherosclerosis research; and magnetic resonance imaging can detect differences in characteristics in lesions undergoing regression.