Expression of circulating microRNA-182,CITED2 and HIF-1 in ischemic cardiomyopathy and their correlation
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摘要: 目的:探讨microRNA-182(miR-182)、cAMP应答元件结合蛋白反式作用因子(CITED2)及低氧诱导因子-1(HIF-1)在缺血性心肌病(ICM)患者外周血中的表达及相关性。方法:收集本院46例ICM患者设为ICM组,同期选择32例健康者为对照组。分析2组一般资料及心脏功能指标[氨基末端B型脑钠肽前体(NT-proBNP)、左室射血分数(LVEF)、6min步行实验(6MWT)距离];用实时荧光定量聚合酶链式反应法(qRT-PCR)检测血浆miR-182的含量,采用ELISA法测定血清CITED2和HIF-1水平,并观察ICM组治疗前及治疗3个月后上述指标的变化;分析ICM患者血浆miR-182水平与有关因素的相关性。结果:ICM 组治疗前CITED2、LVEF及6MWT距离明显低于对照组,NT-proBNP、HIF-1及miR-182表达明显高于对照组,差异均有统计学意义(P<0.01)。与ICM组治疗前比较,ICM组治疗后CITED2、LVEF及6MWT距离明显升高,NT-proBNP、HIF-1及miR-182显著降低,差异均有统计学意义(P<0.01)。ICM组治疗前血浆miR-182的水平与CITED2、LVEF及6MWT距离成负相关(r=-0.427、-0.351、-0.298,P<0.05);ICM组治疗前血浆miR-182水平与HIF-1成正相关(r=0.337,P<0.05)。结论:外周血miR-182水平可作为ICM诊断及进行风险评估的生物标志物。miR-182可能通过其靶蛋白CITED2上调HIF-1,参与调控ICM的发生及发展。
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关键词:
- 缺血性心肌病 /
- microRNA-182 /
- cAMP应答元件结合蛋白反式作用因子 /
- 低氧诱导因子-1
Abstract: Objective:To explore the expression of circulating microRNA-182 (miR-182),CBP/p300 interacting transactivators with ED -rich termini 2 (CITED2), hypoxia-inducible factor-1(HIF-1) in ischemic cardiomyopathy (ICM),and to study their correlation. Method: Thirty two healthy volunteers and 46 ICM patients were enrolled,and their general clinical data and cardiac functional parameters, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF) and the 6-minute walk test (6MWT) distance, were analyzed.The levels of blood plasma miR-182 in all subjects were detected by real time quantitative polymerase chain reaction (qRT-PCR). Serum levels of CITED2 and HIF-1 were detected by enzyme linked immunosorbent assay (ELISA), and their correlation with miR-182 was analyzed. Treatment lasted for 3 months. Level of NT-proBNP, CITED2, HIF-1, miR-182, 6MWT and LVEF in ICM group were observed before and after treatment.Result:Before treatment, the 6MWT distance, LVEF and CITED2 levels in ICM group were significantly lower than those in the control group(P<0.01). The NT-proBNP、HIF-1 and miR-182 levels in ICM group were significantly higher than those in the control group (P<0.01). After 3 months treatment, level of CITED2, 6 min walk distance and LVEF of patients in ICM group were significantly increased (P<0.01), and level of plasma NT-proBNP HIF-1 and miR-182 in ICM group were significantly decreased (P<0.01).Plasma miR-182 was negatively correlated with CITED2, LVEF and the 6MWT distance in group ICM (r=-0.427,-0.351,-0.298,P<0.05). Plasma miR-182 was positively correlated with HIF-1 in group ICM (r=0.337,P<0.05 ). Conclusion:Circulating miR-182 can be used as a new biomarker for ICM diagnosis and its risk evaluation.MiR-182 may upregulate the expression of HIF-1 by depressing CITED2,which might play an important role in the pathogenesis of ICM. [JP]-
Key words:
- ischemic cardiomyopathy /
- microRNA-182 /
- CITED2 gene /
- hypoxia-inducible factor-1
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