*Diabetic Complications Group, Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC 8008, Australia.
Clin Sci (Lond). 2014 Oct;127(7):485-97. doi: 10.1042/CS20140045.
RAGE (receptor for advanced glycation end-products) is expressed on multiple cell types implicated in the progression of atherosclerosis and plays a role in DAA (diabetes-associated atherosclerosis). The aim of the present study was to determine the relative role of either BM (bone marrow)- or non-BM-derived RAGE in the pathogenesis of STZ (streptozotocin)-induced DAA. Male ApoE (apolipoprotein E)-null (ApoE-/-:RAGE+/+) and ApoE:RAGE-null (ApoE-/-:RAGE-/-) mice at 7 weeks of age were rendered diabetic with STZ. At 8 weeks of age, ApoE-/- and ApoE-/-:RAGE-/- control and diabetic mice received BM from either RAGE-null or RAGE-bearing mice, generating various chimaeras. After 10 and 20 weeks of diabetes, mice were killed and gene expression and atherosclerotic lesion formation were evaluated respectively. Deletion of RAGE in either the BM cells or non-BM cells both resulted in a significant attenuation in DAA, which was associated with reduced VCAM-1 (vascular cell adhesion molecule-1) expression and translated into reduced adhesion in vitro. In conclusion, the results of the present study highlight the importance of both BM- and non-BM-derived RAGE in attenuating the development of DAA.
RAGE（晚期糖基化终产物受体）在多种参与动脉粥样硬化进展的细胞类型上表达，并在 DAA（糖尿病相关动脉粥样硬化）中发挥作用。本研究的目的是确定 BM（骨髓）或非 BM 来源的 RAGE 在 STZ（链脲佐菌素）诱导的 DAA 发病机制中的相对作用。7 周龄雄性 ApoE（载脂蛋白 E）缺失（ApoE-/-：RAGE+/+）和 ApoE：RAGE 缺失（ApoE-/-：RAGE-/-）小鼠用 STZ 致糖尿病。在 8 周龄时，ApoE-/-和 ApoE-/-：RAGE-/-对照和糖尿病小鼠接受来自 RAGE 缺失或 RAGE 携带小鼠的 BM，产生各种嵌合体。在糖尿病 10 和 20 周后，处死小鼠并分别评估基因表达和动脉粥样硬化病变形成。在 BM 细胞或非 BM 细胞中缺失 RAGE 均导致 DAA 显著减弱，这与 VCAM-1（血管细胞黏附分子-1）表达减少有关，并转化为体外黏附减少。总之，本研究的结果强调了 BM 和非 BM 来源的 RAGE 在减轻 DAA 发展中的重要性。
