Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known. We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; = 25) and moderate dose (20 mg simvastatin, given the day after PCI; = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed. (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of β-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. iii DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC. Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients

中文翻译：

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高剂量他汀类药物治疗可减少急性心肌梗死后的循环 Dickkopf-1

Dickkopf (DKK) 家族的分泌糖蛋白会改变 Wnt 信号传导，并可能影响斑块不稳定，但他汀类药物对 MI 患者的调节作用尚不清楚。我们测量了急性 ST 段抬高型心肌梗死 (STEMI) 患者在经皮冠状动脉介入治疗 (PCI) 前以及接受短期高剂量（40 mg）治疗后 2、7 天和 2 个月后的血浆 DKK-1 和 DKK-3。瑞舒伐他汀，PCI 前给予；= 25）和中等剂量（20 mg 辛伐他汀，PCI 后一天给予；= 34）。评估了他汀类药物对人脐静脉内皮细胞 (HUVEC) 中 DKK-1 的体外调节作用。 (i) 接受高剂量瑞舒伐他汀的患者在第 2 天 DKK-1 显着下降，并且在整个研究期间一直保持这种下降。然而，辛伐他汀组更普遍使用 β 受体阻滞剂，这可能导致这些患者的 DKK-1 水平较高。 (ii) 在接受高剂量瑞舒伐他汀治疗的患者中，基线 DKK-1 水平与 DKK-1 从基线到第 2 天的变化之间存在很强的相关性。 iii 两个治疗组的 DKK-3 在第 2 天增加，但在 2 个月时恢复到基线水平。 (iv) 他汀类药物治疗剂量依赖性地降低 HUVEC 中的 DKK-1 mRNA 和蛋白质水平。我们的研究结果表明，用 40 mg 瑞舒伐他汀进行高剂量他汀治疗可以持续下调 DKK-1 水平，即使在 STEMI 患者初次事件后 2 个月也是如此