Elevated release of sCD40L from platelets of diabetic patients by thrombin, glucose and advanced glycation end products.
Elevated release of sCD40L from platelets of diabetic patients by thrombin, glucose and advanced glycation end products.
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DOI：
10.3132/dvdr.2005.014
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发表时间：
2005-05-01
影响因子：
2.4
通讯作者：
Schonbeck, Uwe
中科院分区：
文献类型：
--
作者：
Varo, Nerea;Libby, Peter;Schonbeck, Uwe
促炎性CD 40/CD 40 L二联体参与动脉粥样硬化的形成。可溶性配体（sCD 40 L）的血浆水平可预测心血管事件，并且在糖尿病患者中升高。本研究比较了糖尿病患者和对照组血小板和T淋巴细胞表面CD 40/CD 40 L的表达，并检测了葡萄糖和晚期糖基化终产物（AGEs）是否刺激sCD 40 L的释放。糖尿病患者（n = 9）和对照组（n = 13）血小板或T淋巴细胞上CD 40/CD 40 L的组成型和诱导型表面表达无差异。糖尿病患者的血小板含有比对照组更高的细胞内CD 40 L（p < 0.05），并且与对照组（3.64 +/- 2.03 ng/ml; p < 0.05）相比，糖尿病患者中凝血酶刺激更大的血小板sCD 40 L释放（15.11 +/- 16.77 ng/ml）。葡萄糖和AGEs诱导小鼠血小板sCD 40 L释放和巨核细胞CD 40 L表达。本研究证实了糖尿病患者血小板中CD 40 L含量升高和诱导释放，并确定葡萄糖和AGEs作为这些患者中sCD 40 L血浆水平升高的表达和释放的潜在触发因素。
The pro-inflammatory CD40/CD40L dyad participates in atherogenesis. Plasma levels of the soluble ligand (sCD40L) predict cardiovascular events and are elevated in diabetic patients. This study compared CD40/CD40L surface expression on platelets and T lymphocytes of diabetic and control subjects, and tested whether glucose and advanced glycation end products (AGEs) stimulate sCD40L release. Constitutive and inducible surface expression of CD40/CD40L on platelets or T lymphocytes did not differ between diabetic patients (n = 9) and controls (n = 13). Platelets from diabetic patients contained higher intracellular CD40L than controls (p < 0.05) and thrombin stimulated greater platelet sCD40L release in diabetic patients (15.11 +/- 16.77 ng/ml) compared to controls (3.64 +/- 2.03 ng/ml; p < 0.05). Glucose and AGEs induced platelet sCD40L release and CD40L expression in mouse megakaryocytes. This study demonstrates elevated CD40L content and inducible release from platelets of diabetic patients, and identifies glucose and AGEs as potential triggers of expression and release accounting for the elevated sCD40L plasma levels in these patients.