Babaei Saeid, Stewart Duncan J, Picard Pierre, Monge Juan Carlos
Terrence Donnelly Vascular Biology Laboratory, Terrence Donnelly Heart Center, Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto Ont., Canada M5B 1W8.
Atherosclerosis. 2002 May;162(1):45-53. doi: 10.1016/s0021-9150(01)00680-3.
VasoCare therapy, which involves the administration of autologous blood following the ex vivo exposure to physico-chemical stressors, has been shown to modulate immune responses. Since immune mechanisms have been recognized to be pivotal in the pathogenesis of atherosclerosis, we hypothesized that VasoCare treatment would inhibit atherosclerosis in LDL-R (-/-) mice. Three groups of LDL-R (-/-) mice were studied: a control group that was fed normal chow (Group I) and no other treatment; a control group that received a high cholesterol (HC) diet for 8 weeks (group II) with sham saline injections; and a third group (III) that received HC diet for 8 weeks and VasoCare treatment initiated after four weeks of HC feeding. Atherosclerotic area (AA), relative to total aortic area (TA), was assessed after 8 weeks of HC feeding by oil red O staining, and cross sectional plaque area at the level of the aortic valve leaflets was determined by quantitative morphometry. HC mice exhibited substantial aortic lipid deposition which was profoundly reduced in the VasoCare treated animals (AA/TA ratios in group II: 0.32+/-0.15 vs. group III: 0.17+/-0.06; P<0.05). This was associated with a significant decrease in cross sectional area of plaque in the aortic sinuses. VasoCare therapy also reduced the xanthoma formation and limb swelling characteristic of this animal model. However, cholesterol levels, measured by an enzymatic assay, showed similar marked increases in total serum cholesterol (CHO) in the animals receiving HC diet alone and those receiving the HC diet and VasoCare treatment [group I: 5.4+/-0.8 mM, group II: 46.7+/-3.6 mM, and group III: 44.7+/-2.8 mM (P<0.01 vs. group I)]. We conclude that VasoCare treatment inhibits progression of atherosclerotic lesions in a murine model of human familial hypercholesterolemia by a mechanism independent of cholesterol lowering.
血管护理疗法是在体外暴露于物理化学应激源后给予自体血液,已被证明可调节免疫反应。由于免疫机制在动脉粥样硬化发病机制中被认为至关重要,我们推测血管护理治疗会抑制低密度脂蛋白受体基因敲除(LDL-R (-/-))小鼠的动脉粥样硬化。研究了三组LDL-R (-/-)小鼠:一组为对照组,喂食普通饲料(第一组)且未接受其他治疗;另一对照组接受高胆固醇(HC)饮食8周(第二组),并进行假生理盐水注射;第三组(第三组)接受HC饮食8周,并在HC喂养4周后开始血管护理治疗。在HC喂养8周后,通过油红O染色评估相对于主动脉总面积(TA)的动脉粥样硬化面积(AA),并通过定量形态学确定主动脉瓣叶水平的横截面斑块面积。HC小鼠表现出大量主动脉脂质沉积,而在接受血管护理治疗的动物中这种沉积显著减少(第二组AA/TA比值:0.32±0.15,第三组:0.17±0.06;P<0.05)。这与主动脉窦中斑块横截面面积的显著减小有关。血管护理疗法还减少了该动物模型特有的黄色瘤形成和肢体肿胀。然而,通过酶法测定的胆固醇水平显示,仅接受HC饮食的动物和接受HC饮食及血管护理治疗的动物血清总胆固醇(CHO)均有类似的显著升高[第一组:5.4±0.8 mM,第二组:46.7±3.6 mM,第三组:44.7±2.8 mM(与第一组相比P<0.01)]。我们得出结论,血管护理治疗通过一种不依赖于降低胆固醇的机制抑制人类家族性高胆固醇血症小鼠模型中动脉粥样硬化病变的进展。