Moheimani Fatemeh, Tan Joanne T M, Brown Bronwyn E, Heather Alison K, van Reyk David M, Davies Michael J
Free Radical Group, The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia.
Exp Diabetes Res. 2011;2011:851280. doi: 10.1155/2011/851280. Epub 2011 Aug 28.
During atherosclerosis monocyte-derived macrophages accumulate cholesteryl esters from low-density lipoproteins (LDLs) via lectin-like oxidised LDL receptor-1 (LOX-1) and class AI and AII (SR-AI, SR-AII) and class B (SR-BI, CD36) scavenger receptors. Here we examined the hypothesis that hyperglycaemia may modulate receptor expression and hence lipid accumulation in macrophages. Human monocytes were matured into macrophages in 30 versus 5 mM glucose and receptor expression and lipid accumulation quantified. High glucose elevated LOX1 mRNA, but decreased SR-AI, SR-BI, LDLR, and CD36 mRNA. SR-BI and CD36 protein levels were decreased. Normo- and hyperglycaemic cells accumulated cholesteryl esters from modified LDL to a greater extent than control LDL, but total and individual cholesteryl ester accumulation was not affected by glucose levels. It is concluded that, whilst macrophage scavenger receptor mRNA and protein levels can be modulated by high glucose, these are not key factors in lipid accumulation by human macrophages under the conditions examined.
在动脉粥样硬化过程中，单核细胞衍生的巨噬细胞通过凝集素样氧化型低密度脂蛋白受体-1（LOX-1）、A类I型和II型（SR-AI、SR-AII）以及B类（SR-BI、CD36）清道夫受体从低密度脂蛋白（LDL）中积累胆固醇酯。在此，我们检验了高血糖可能调节受体表达并因此调节巨噬细胞脂质积累的假说。将人单核细胞在30 mM葡萄糖与5 mM葡萄糖条件下培养成熟为巨噬细胞，并对受体表达和脂质积累进行定量分析。高糖使LOX1 mRNA升高，但使SR-AI、SR-BI、LDLR和CD36 mRNA降低。SR-BI和CD36蛋白水平降低。正常血糖和高血糖细胞从修饰型LDL中积累胆固醇酯的程度大于对照LDL，但总胆固醇酯积累和单个胆固醇酯积累不受葡萄糖水平影响。得出的结论是，虽然高糖可调节巨噬细胞清道夫受体的mRNA和蛋白水平，但在所研究的条件下，这些并非人类巨噬细胞脂质积累的关键因素。
