Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia.
Dose-dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia.
复制标题
DOI：
10.1186/2001-1326-1-23
复制
发表时间：
2012-10-06
影响因子：
10.6
通讯作者：
Keeley EC
中科院分区：
文献类型：
--
作者：
Camnitz W;Burdick MD;Strieter RM;Mehrad B;Keeley EC
HMG-CoA 还原酶抑制剂（他汀类药物）具有与降低胆固醇无关的多效性作用，包括对血管生成的剂量依赖性作用。血管生成在慢性缺血心肌的血管化和动脉粥样硬化斑块的稳定中发挥着关键作用。趋化因子是结构相关的细胞因子分子家族，发挥多种生物学功能，包括控制血管生成。他汀类药物治疗对血管生成和血管抑制趋化因子的影响尚未得到广泛评估。我们试图检验这样的假设：在高脂血症受试者中，他汀类药物治疗以剂量依赖性方式影响血管生成和血管抑制趋化因子的血浆水平。我们前瞻性地收集了有高脂血症史、未经治疗或正在接受他汀类药物治疗的受试者的人口统计、血管造影和实验室数据。获得外周血样本用于测量血浆血管生成和血管抑制趋化因子。使用逻辑回归进行多变量分析，调整以下变量：年龄、性别、既往心肌梗塞以及长期服用阿司匹林、氯吡格雷、胰岛素、口服降糖药、β-受体阻滞剂和钙通道阻滞剂。纳入了 168 名接受他汀类药物治疗的患者（48 名低剂量患者，定义为 <10mg 阿托伐他汀当量，120 名高剂量患者，定义为≥10mg 阿托伐他汀当量剂量）和来自同一数据库的 11 名有高脂血症史但未服用他汀类药物的受试者。各组之间的基线人口统计学、合并症、脂质组、其他药物或血管造影数据没有显着差异。各组间血管生成趋化因子 CXCL1 和 CXCL12 水平存在显着差异。未接受他汀类药物治疗的受试者中 CXCL1 的中位水平最高。与未接受他汀类药物治疗或使用低剂量他汀类药物的受试者相比，服用高剂量他汀类药物的受试者的 CXCL12 中位值较低（2316 [2255–11071]、vs 2362 [2016–10622]、vs 2189 [1968–2705] pg/mL，p=0.042）。在多变量分析中，CXCL12 仍然是唯一与他汀类药物剂量呈 95% 水平呈强烈负相关的因素 (p=0.011)。与不治疗或低剂量他汀类药物治疗相比，高剂量 HMG-CoA 还原酶抑制剂治疗与高脂血症受试者循环 CXCL12 水平降低相关，并且 CXCL12 与他汀类药物剂量呈强烈负相关。需要进行更多研究来在其他队列中证实这一发现，并确定高剂量他汀类药物是否会影响患者的血管生成。
HMG-CoA reductase inhibitors (statins) have pleiotropic effects that are independent of cholesterol-lowering, including a dose-dependent effect on angiogenesis. Angiogenesis plays a critical role both in vascularization of the chronically ischemic myocardium and in stabilization of atherosclerotic plaques. Chemokines, a family of structurally-related cytokine molecules, exert diverse biological functions including control of angiogenesis. The effect of statin therapy on angiogenic and angiostatic chemokines has not been evaluated extensively. We sought to test the hypothesis that, in subjects with hyperlipidemia, statin therapy influences plasma levels of angiogenic and angiostatic chemokines in a dose-dependent manner. We prospectively collected demographic, angiographic and laboratory data from subjects with a history of hyperlipidemia who were either untreated or on statin therapy. A peripheral blood sample was obtained for measurement of plasma angiogenic and angiostatic chemokines. Multivariable analysis using logistic regression was performed adjusting for the following variables: age, gender, prior myocardial infarction, and chronic administration of aspirin, clopidogrel, insulin, oral hypoglycemic agents, beta-blockers and calcium channel blockers. 168 patients on statin therapy (48 on low-dose, defined as <10mg atorvastatin-equivalent, and 120 on high-dose, defined as ≥10mg atorvastatin-equivalent dose) and 11 subjects from the same database who had a history of hyperlipidemia but who were not on statins were enrolled. There were no significant differences in baseline demographics, co-morbidities, lipid panels, other medications, or angiographic data between the groups. The angiogenic chemokines CXCL1 and CXCL12 levels were significantly different across the groups. Median levels of CXCL1 were highest in subjects not on statin therapy. Compared to subjects either not on statin therapy or on low-dose statins, those taking high-dose statins had lower median values of CXCL12 (2316 [2255–11071], vs 2362 [2016–10622], vs 2189 [1968–2705] pg/mL, p=0.042). On multivariate analysis, CXCL12 remained the only factor that was strongly and inversely associated with statin dose at the 95% level (p=0.011). Compared to no therapy or low-dose statin therapy, treatment with high-doses of HMG-CoA reductase inhibitors is associated with decreased circulating CXCL12 levels in subjects with hyperlipidemia, and CXCL12 is strongly and inversely associated with statin dose. Additional studies are needed to confirm this finding in other cohorts and to determine if high-dose statins affect angiogenesis in patients.