UMR INSERM 1060/Université de Lyon, Cardiovasculaire, Métabolisme, Diabétologie, et Nutrition (CarMeN), INSA-Lyon, IMBL, Bât. Louis Pasteur, 20 av. Albert Einstein, 69621 Villeurbanne, France.
Diabetologia. 2011 Nov;54(11):2931-40. doi: 10.1007/s00125-011-2272-8. Epub 2011 Aug 17.
AIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups.
The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated.
Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A(2), and through increased thromboxane B(2) formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets.
CONCLUSIONS/INTERPRETATION: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation.
目的/假设：本研究评估了代谢综合征肥胖患者的 LDL 中的氧化应激，并将其与 2 型糖尿病患者或对照志愿者的 LDL 进行了比较。还测定了三组 LDL 对血小板的影响。
从代谢综合征患者、2 型糖尿病患者和志愿者的血浆中分离 LDL，测定其脂质、脂肪酸和脂肪酸氧化产物的图谱（每组 10 例）。研究了来自各组 LDL 对血小板花生四烯酸信号级联和聚集的影响。
与对照志愿者的 LDL 相比，肥胖代谢综合征和 2 型糖尿病患者的胆固醇酯水平较低，三酰甘油水平较高，乙醇胺溶血磷脂水平较低。两组患者的 LDL 中，亚油酸在磷脂酰胆碱和胆固醇酯中的比例降低。在脂质过氧化的标志物中，代谢综合征和 2 型糖尿病患者的 LDL 中，亚油酸的氧化产物（羟基十八碳二烯酸）和丙二醛分别增加了 59%和两倍。代谢综合征和 2 型糖尿病患者的 LDL 通过增加 p38 丝裂原活化蛋白激酶和胞质型磷脂酶 A2 的磷酸化，以及增加血栓素 B2 的形成，同等程度地激活血小板花生四烯酸信号级联。来自代谢综合征和 2 型糖尿病患者的 LDL 分别使血小板聚集增加了三倍和 3.5 倍，而对照 LDL 对血小板没有激活作用。
结论/解释：肥胖患者的代谢综合征，无论是否伴有糖尿病，都与 LDL 中氧化应激的增加有关，这种应激会触发血小板的激活。
