Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: A dose-response effect dependent on endothelial nitric oxide synthase
Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: A dose-response effect dependent on endothelial nitric oxide synthase
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DOI：
10.1016/j.ijcard.2007.10.044
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发表时间：
2009-01-24
影响因子：
3.5
通讯作者：
Luo, Yu
中科院分区：
文献类型：
--
作者：
Chen, Hong;Ren, Jing-Yi;Luo, Yu
背景：冠心病(CAD)患者存在内皮功能受损。辛伐他汀治疗已被证明能显著改善这些患者的内皮功能。尽管停用他汀类药物在临床上是一个常见的问题，但停用他汀类药物对冠心病患者血管内皮功能的影响在很大程度上尚不清楚。目的：研究辛伐他汀停药后对冠心病患者肱动脉内皮功能的影响及其机制。用辛伐他汀20 mg治疗4周。在基础状态、辛伐他汀治疗4周和治疗结束后1周，使用高分辨率超声评估肱动脉内皮依赖性血流介导的血管扩张(FMD)。20例健康受试者作为对照组。此外，我们研究了人脐静脉内皮细胞(HUVECs)在第2-3代融合单层的潜在机制。用辛伐他汀处理人脐静脉内皮细胞。24 h后，反复冲洗细胞以去除药物，并在指定的时间点收集条件培养液。结果：(1)停用辛伐他汀1周内，患者血清总胆固醇(21.3%)和低密度脂蛋白(18.2%)均有回升，但仍低于基础值(P
Background: Patients with coronary artery disease (CAD) have impaired endothelial function. Simvastatin therapy has been demonstrated to significantly improve endothelial function in these patients. Although withdrawal of statins is a frequent problem in clinical practice, the effects after discontinuation of statins treatment on endothelial function in patients with CAD are largely unknown.Objective: This study investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients with CAD and the underlying mechanisms.Methods: We recruited 30 patients with established CAD. They were treated with 20 mg simvastatin for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed in the brachial artery using high-resolution ultrasound at baseline, 4 weeks during simvastatin treatment, and 1 week after termination of therapy. 20 healthy subjects were also studied as a control group. Furthermore, we investigated underlying mechanisms on human umbilical vein endothelial cells (HUVECs) confluent monolayers at passages 2-3. HUVECs were exposed to simvastatin. After 24 h cells were repeatedly washed to remove the drugs, and the conditioned mediums were collected at the indicated time points. The nitric oxide (NO) production and levels of eNOS mRNA after 24 h of withdrawal of statins were examined.Results: (1) Abrupt discontinuation of simvastatin treatment leads to a rebound of serum total cholesterol (21.3%) and LDL cholesterol (18.2%) in patients within 1 week, but they were still lower than the baseline values (P