Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.
Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.
复制标题
急性高糖性血症诱导血小板多动，而多囊卵巢综合征中胰岛素不会减弱。
DOI：
10.1161/jaha.113.000706
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发表时间：
2014-02-28
影响因子：
5.4
通讯作者：
Atkin SL
中科院分区：
文献类型：
--
作者：
Aye MM;Kilpatrick ES;Aburima A;Wraith KS;Magwenzi S;Spurgeon B;Rigby AS;Sandeman D;Naseem KM;Atkin SL
动脉粥样硬化血栓形成与血小板过度活跃有关。多囊卵巢综合征（PCOS）的临床特点是高脂血症和胰岛素抵抗（IR）。在年轻的PCOS女性中检测诱导的高胆固醇血症对IR和血小板功能的影响。在禁食过夜后，13名PCOS和12名健康女性在不同的日子里分别输注生理盐水或20%胰岛素5小时。在每次输注的最后2小时，使用高胰岛素正常血钳夹测量胰岛素敏感性。使用每次输注期间（2小时）和每次钳夹结束时采集的全血，通过血小板纤维蛋白原结合和P-选择素表达的流式细胞术分析，测量血小板对二磷酸腺苷（ADP）和前列环素（PGI 2）的反应。在对照组（中位数，四分位数间距）（5.25 [3.3，6.48] vs 2.60 [0.88，3.88] mg kg−1 min−1，P<0.001）和PCOS组（3.15 [2.94，3.85] vs 1.06 [0.72，1.43] mg kg−1 min−1，P<0.001）中，脂质输注增加甘油三酯并降低胰岛素敏感性。与生理盐水相比，两组在脂质输注过程中ADP对血小板活化的作用增强，而PGI 2对血小板活化的抑制作用减弱。重要的是，胰岛素输注通过降低脂质诱导的血小板对1 μmol/L ADP的反应来降低其活性（78.7% [67.9，82.3] vs 62.8% [51.8，73.3]，P=0.02），对0.01 μmol/L PGI 2的敏感性增加对照组为67.6% [39.5，83.8] vs 40.9% [23.8，60.9]，P=0.01，但PCOS组无。与对照组相比，两组中急性高胰岛素血症诱导IR和血小板活化增加，PCOS受试者中胰岛素不能逆转。这表明急性高脂血症和IR诱导的血小板过度活化可能导致动脉粥样硬化血栓形成风险。URL：www.isrctn.org。唯一标识符：ISRCTN 42448814。
Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P‐selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg−1 min−1, P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg−1 min−1, P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid‐induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero‐thrombotic risk. URL: www.isrctn.org. Unique Identifier: ISRCTN42448814.