Reis E D, Li J, Fayad Z A, Rong J X, Hansoty D, Aguinaldo J G, Fallon J T, Fisher E A
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
J Vasc Surg. 2001 Sep;34(3):541-7. doi: 10.1067/mva.2001.115963.
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.
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.
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.
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.
动脉粥样硬化病变的消退是一个重要目标。尚无广泛的实验证据表明晚期病变能够实现消退。为研究这一问题，我们建立了一个模型，以维持高脂血症（载脂蛋白E [apoE] 缺陷）小鼠晚期动脉病变血浆脂蛋白环境的长期变化。
在典型西方饮食喂养38周后，apoE缺陷小鼠（血浆总胆固醇为1334±219 [±SEM] mg/dL）在整个动脉树中出现了晚期动脉粥样硬化病变（即超过巨噬细胞泡沫细胞阶段）。将含有病变的胸主动脉移植（替换腹主动脉的一段）到apoE缺陷或野生型（WT）（总胆固醇为86±10 mg/dL）受体小鼠体内。9周后收获移植血管。
与移植前病变（面积 = 0.0892±0.0179 mm²）相比，apoE缺陷小鼠到apoE缺陷小鼠的移植血管病变大小有增加趋势（0.2411±0.0636 mm²；P = 0.06），而apoE缺陷小鼠到WT小鼠的移植血管病变则显著减小（0.0214±0.0049 mm²；P < 0.001）。此外，apoE缺陷小鼠到WT小鼠的移植血管中没有泡沫细胞，但在移植前病变以及apoE缺陷小鼠到apoE缺陷小鼠的移植血管中泡沫细胞丰富。通过磁共振成像对移植血管进行体内无创评估，在apoE缺陷小鼠到apoE缺陷小鼠组中检测到血管壁增厚。
血浆脂蛋白谱持续正常化可使晚期动脉粥样硬化病变几乎完全消退。小鼠同基因动脉移植是一种用于动脉粥样硬化研究的新型且有价值的模型系统；磁共振成像可检测正在消退的病变特征差异。
