Servicio de Bioquímica, Clínica Universitaria de Navarra, Avda Pío XII 36, 31008 Pamplona, Spain.
Am J Physiol Endocrinol Metab. 2010 May;298(5):E1072-7. doi: 10.1152/ajpendo.00728.2009. Epub 2010 Mar 2.
The proinflammatory and proatherogenic mediator, soluble CD40 ligand (CD40L), is increased in the metabolic syndrome (MS) and released from platelets. We hypothesized that adiponectin modulates platelet function, and we sought to evaluate the association of adiponectin and sCD40L levels with platelet aggregation in MS and the effects of adiponectin on platelet aggregation and activation. Platelet aggregation and circulating adiponectin, sCD40L and P-selectin were determined in 30 controls and 30 patients with MS. Also, in vitro studies were performed in platelet-rich plasma from nine healthy volunteers. Adiponectin receptors were demonstrated by Western blotting and flow cytometry. ADP and epinephrine platelet aggregation was measured after preincubation with adiponectin. sCD40L and P-selectin secretion was measured in the supernatants by ELISA. Patients with MS had higher sCD40L and P-selectin than controls (5.96 +/- 0.50 vs. 4.28 +/- 0.41 ng/ml, P < 0.05, and 151 +/- 8 vs. 122 +/- 9 ng/ml, P < 0.05). By contrast, adiponectin was lower in patients with MS than in controls (5.25 +/- 0.30 vs. 7.35 +/- 0.34 microg/ml, P < 0.001). Higher platelet aggregation was found in MS. Adiponectin inversely correlated with P-selectin (R = -0.35, P = 0.009), sCD40L (r = -0.24, P = 0.05) and epinephrine and collagen induced aggregation (r = -0.80, P = 0.005; r = -0.70, P = 0.011). Platelets express the receptors for adiponectin. Platelet aggregatory response to epinephrine and ADP significantly decreased following preincubation with adiponectin (96 +/- 4 vs. 23 +/- 3%, P < 0.001, and 102 +/- 9 vs. 85 +/- 9%, P = 0.004). Adiponectin prevented platelet sCD40L release (1.63 +/- 0.15 vs. 2.04 +/- 0.20 ng/ml, P < 0.001). Enhanced platelet aggregation and activation markers are found in MS associated with low adiponectin concentrations. Novel evidence is provided demonstrating that adiponectin has antithrombotic properties, since it inhibits platelet aggregation and platelet activation.
促炎和动脉粥样硬化介质可溶性 CD40 配体（CD40L）在代谢综合征（MS）中增加，并从血小板中释放。我们假设脂联素调节血小板功能，并寻求评估脂联素和 sCD40L 水平与 MS 血小板聚集的关系，以及脂联素对血小板聚集和激活的影响。在 30 名对照者和 30 名 MS 患者中测定血小板聚集和循环脂联素、sCD40L 和 P-选择素。此外，在来自 9 名健康志愿者的富含血小板的血浆中进行了体外研究。通过 Western blot 和流式细胞术证明了脂联素受体。在用脂联素预孵育后，测量 ADP 和肾上腺素诱导的血小板聚集。通过 ELISA 测量上清液中 sCD40L 和 P-选择素的分泌。与对照组相比，MS 患者的 sCD40L 和 P-选择素更高（5.96 +/- 0.50 与 4.28 +/- 0.41ng/ml，P < 0.05，和 151 +/- 8 与 122 +/- 9ng/ml，P < 0.05）。相比之下，MS 患者的脂联素低于对照组（5.25 +/- 0.30 与 7.35 +/- 0.34ug/ml，P < 0.001）。在 MS 中发现了更高的血小板聚集。脂联素与 P-选择素呈负相关（R = -0.35，P = 0.009），与 sCD40L（r = -0.24，P = 0.05）和肾上腺素及胶原诱导的聚集呈负相关（r = -0.80，P = 0.005；r = -0.70，P = 0.011）。血小板表达脂联素受体。在用脂联素预孵育后，肾上腺素和 ADP 诱导的血小板聚集反应明显降低（96 +/- 4 与 23 +/- 3%，P < 0.001，和 102 +/- 9 与 85 +/- 9%，P = 0.004）。脂联素可防止血小板 sCD40L 释放（1.63 +/- 0.15 与 2.04 +/- 0.20ng/ml，P < 0.001）。在与低脂联素浓度相关的 MS 中发现增强的血小板聚集和激活标志物。提供了新的证据证明，脂联素具有抗血栓形成特性，因为它抑制血小板聚集和血小板激活。
