Laboratory of Renal and Vascular Biology, Department of Nephrology and Hypertension, F03.227, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Atherosclerosis. 2013 Feb;226(2):341-7. doi: 10.1016/j.atherosclerosis.2012.11.017. Epub 2012 Nov 23.
Atherosclerotic plaque development is accelerated in patients with diabetes. Bone marrow-derived smooth muscle-like cells have been detected in neointima and diabetes has a numerical and functional effect on circulating vascular progenitor cells. We hypothesized that an increased number of bone marrow-derived smooth muscle-like cells correlates with accelerated atherosclerosis in diabetic apoE-deficient mice.
ApoE(-/-) mice were subjected to total body irradiation and transplanted with bone marrow cells from GFP-transgenic mice. Mice were rendered diabetic by streptozotocin injection and examined after 4, 8, 11 and 15 weeks of diabetes.
Diabetic mice showed a larger plaque area and a higher number of smooth muscle-like cells compared to non-diabetic mice at 11 and 15 weeks after diabetes induction. Bone marrow-derived smooth muscle-like cells were detected in atherosclerotic plaques of both diabetic and control mice, but numbers were higher in plaques of diabetic mice 11 weeks after induction of diabetes. The higher number of bone marrow-derived smooth muscle-like cells in plaque was associated with an increase in in vitro differentiation of smooth muscle-like cells from spleen mononuclear cells in diabetic mice.
Diabetes increases the number of bone marrow-derived smooth muscle-like cells in atherosclerotic plaques and the differentiation of mononuclear cells towards smooth muscle-like cells, which may contribute to accelerated atherosclerotic plaque development in diabetic apoE(-/-) mice.
糖尿病患者的动脉粥样硬化斑块发展加速。在新生内膜中已经检测到骨髓衍生的平滑肌样细胞，并且糖尿病对循环血管祖细胞具有数量和功能上的影响。我们假设骨髓衍生的平滑肌样细胞数量增加与糖尿病 apoE 缺陷小鼠的动脉粥样硬化加速有关。
apoE(-/-)小鼠接受全身放射和 GFP 转基因小鼠的骨髓细胞移植。通过链脲佐菌素注射使小鼠发生糖尿病，并在糖尿病诱导后 4、8、11 和 15 周进行检查。
与非糖尿病小鼠相比，糖尿病小鼠在糖尿病诱导后 11 和 15 周时表现出更大的斑块面积和更多的平滑肌样细胞。在糖尿病和对照组小鼠的动脉粥样硬化斑块中均检测到骨髓衍生的平滑肌样细胞，但在糖尿病诱导后 11 周的斑块中数量更高。斑块中骨髓衍生的平滑肌样细胞数量增加与糖尿病小鼠脾单核细胞中平滑肌样细胞体外分化增加相关。
糖尿病增加了动脉粥样硬化斑块中骨髓衍生的平滑肌样细胞数量，以及单核细胞向平滑肌样细胞的分化，这可能导致糖尿病 apoE(-/-)小鼠的动脉粥样硬化斑块发展加速。
