Sobenin I A, Tertov V V, Orekhov A N
Institute of Experimental Cardiology, Russian Academy of Medical Sciences, Moscow.
Int Angiol. 1994 Mar;13(1):78-83.
Low density lipoprotein (LDL) from Type 1 and Type 2 diabetic patients, unlike LDL from healthy subjects, caused a 1.5- to 2.5-fold increase in the cholesterol content of cells cultured from unaffected human aortic intima, i.e. possessed atherogenic potential. LDL were further divided into two subfractions by affinity chromatography on Ricinus communis agglutinin-agarose. The amount of bound LDL was significantly higher in diabetic patients as compared with healthy subjects. Bound LDLs differed from unbound ones by significantly lowered sialic acid content, i.e. were desialylated lipoproteins. Desialylated, but not sialylated LDL subfraction induced massive cholesterol accumulation in cultured cells. Desialylated LDL subfraction in diabetic patients was also characterized by a higher degree of nonenzymatic glycation as compared to LDL subfraction with normal sialic acid level. Desialylated LDL had significantly decreased levels of free and esterified cholesterol, triglycerides and phosphatidylcholine and elevated amounts of lysophosphatidylcholine. These disturbances in lipid constituent of LDL were weak in healthy subjects, but conspicuous in diabetic patients. The results of this study have shown that there is in vivo modified LDL subfraction in the blood of diabetic patients which is characterized by crucial changes in protein and lipid moiety and are able to induce massive cholesterol accumulation in cultured cells.
与健康受试者的低密度脂蛋白(LDL)不同,1型和2型糖尿病患者的LDL可使从未受影响的人主动脉内膜培养的细胞中的胆固醇含量增加1.5至2.5倍,即具有致动脉粥样硬化潜力。通过蓖麻凝集素-琼脂糖亲和层析将LDL进一步分为两个亚组分。与健康受试者相比,糖尿病患者中结合的LDL量明显更高。结合的LDL与未结合的LDL不同,其唾液酸含量显著降低,即去唾液酸化脂蛋白。去唾液酸化而非唾液酸化的LDL亚组分在培养细胞中诱导大量胆固醇积累。与唾液酸水平正常的LDL亚组分相比,糖尿病患者中的去唾液酸化LDL亚组分还具有更高程度的非酶糖基化特征。去唾液酸化LDL的游离胆固醇、酯化胆固醇、甘油三酯和磷脂酰胆碱水平显著降低,溶血磷脂酰胆碱含量升高。LDL脂质成分的这些紊乱在健康受试者中较弱,但在糖尿病患者中明显。本研究结果表明,糖尿病患者血液中存在体内修饰的LDL亚组分,其特征是蛋白质和脂质部分发生关键变化,并且能够在培养细胞中诱导大量胆固醇积累。