Santilli Francesca, Davì Giovanni, Consoli Agostino, Cipollone Francesco, Mezzetti Andrea, Falco Angela, Taraborelli Tea, Devangelio Eleonora, Ciabattoni Giovanni, Basili Stefania, Patrono Carlo
Center of Excellence on Aging and Department of Medicine, University of Chieti G. D'Annunzio Schools of Medicine and Pharmacy, Chieti, Italy.
J Am Coll Cardiol. 2006 Jan 17;47(2):391-7. doi: 10.1016/j.jacc.2005.03.079. Epub 2005 Dec 20.
The goals of this study were to characterize the platelet contribution to soluble CD40 ligand (sCD40L), to correlate its formation with the extent of oxidative stress and platelet activation, and to investigate the effects of improved metabolic control and low-dose aspirin on these processes.
Inflammation, oxidative stress, and platelet activation are involved in the pathogenesis of type 2 diabetes (T2DM) and its complications. The CD40-CD40L interactions result in inflammatory and pro-thrombotic responses.
Urinary 8-iso-prostaglandin (PG)F2alpha and 11-dehydro-thromboxane (TX)B2, in vivo markers of oxidative stress and platelet activation, respectively, plasma CD40L, and C-reactive protein (CRP) were measured in 114 T2DM patients and 114 control patients. A randomized, parallel group, 17-day study of aspirin (30, 100, or 325 mg/day) was performed in 18 T2DM patients. A similar study was performed in six healthy volunteers (aspirin, 100 mg/day). Twenty poorly controlled T2DM patients were studied before and after improved metabolic control.
Compared with control patients, diabetic patients showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, sCD40L, and CRP. On multiple regression analysis, 11-dehydro-TXB2 and 8-iso-PGF2alpha excretion rates predicted sCD40L levels. Soluble CD40L linearly correlated with 11-dehydro-TXB2 (rho = 0.67, p < 0.0001), and both were reduced after one week of aspirin (p < 0.0026), with slow recovery over 10 days after aspirin withdrawal. Improved metabolic control was associated with a reduction in sCD40L, 8-iso-PGF2alpha, and 11-dehydro-TXB2.
This study provides several lines of evidence for the dependence of sCD40L release on TXA(2)-dependent platelet activation in T2DM and provides novel mechanistic insight into the amplification loops of persistent platelet activation in this setting.
本研究的目的是描述血小板对可溶性CD40配体（sCD40L）的贡献，将其形成与氧化应激程度和血小板活化相关联，并研究改善代谢控制和低剂量阿司匹林对这些过程的影响。
炎症、氧化应激和血小板活化参与2型糖尿病（T2DM）及其并发症的发病机制。CD40-CD40L相互作用导致炎症和促血栓形成反应。
在114例T2DM患者和114例对照患者中测量尿8-异前列腺素（PG）F2α和11-脱氢血栓烷（TX）B2，分别作为氧化应激和血小板活化的体内标志物、血浆CD40L和C反应蛋白（CRP）。对18例T2DM患者进行了一项为期17天的阿司匹林（30、100或325mg/天）随机、平行组研究。在6名健康志愿者中进行了类似的研究（阿司匹林，100mg/天）。对20例血糖控制不佳的T2DM患者在改善代谢控制前后进行了研究。
与对照患者相比，糖尿病患者的8-异PGF2α、11-脱氢TXB2、sCD40L和CRP水平显著更高。多元回归分析显示，11-脱氢TXB2和8-异PGF2α排泄率可预测sCD40L水平。可溶性CD40L与11-脱氢TXB2呈线性相关（rho = 0.67，p < 0.0001），两者在服用阿司匹林一周后均降低（p < 0.0026），停药后10天缓慢恢复。改善代谢控制与sCD40L、8-异PGF2α和11-脱氢TXB2的降低有关。
本研究为T2DM中sCD40L释放依赖于TXA(2)依赖性血小板活化提供了多条证据，并为这种情况下持续血小板活化的放大环提供了新的机制见解。
