Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients.
Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients.
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DOI：
10.1371/journal.pone.0037000
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kaplan MJ
中科院分区：
文献类型：
--
作者：
Somers EC;Zhao W;Lewis EE;Wang L;Wing JJ;Sundaram B;Kazerooni EA;McCune WJ;Kaplan MJ
系统性红斑狼疮(SLE)患者的心血管(CV)共病显著增加，但Framingham风险评分无法完全解释这一现象。最近来自体外研究的证据表明，I型干扰素(IFN)可促进SLE患者的早发性心血管疾病(CVD)。在一组无明显心血管疾病的狼疮患者中，我们评估了I型干扰素信号与血管损伤的功能和解剖学证据，以及心血管风险的生物标记物的相关性。用实时荧光定量聚合酶链式反应检测95例SLE患者和38例对照组的血清I型干扰素活性(诱导5个干扰素诱导基因；IFIGs)。超声测量肱动脉血流介导性扩张(FMD)和颈动脉内膜中层厚度(CIMT)，CT测量冠状动脉钙化。采用酶联免疫吸附试验检测血清血管生物标志物。我们评估了I型IFN对FMD、CIMT和冠状动脉钙化的影响，方法是首先应用主成分分析将5个IFIG的数据组合成可以同时建模的汇总成分。3个成分解释了IFIG总变异的97.1%。采用多元线性回归分析这三种成分和其他协变量与FMD和CIMT结果之间的关系；采用零膨胀泊松回归对冠状动脉钙化进行建模。在控制了传统的心血管危险因素后，血清干扰素活性的升高与系统性红斑狼疮患者和对照组的内皮功能降低(P<；0.001)、系统性红斑狼疮患者的CIMT增加(P<；1和2)以及冠状动脉钙化的严重程度(P<；3)显著相关。在没有明显心血管病史并且控制了Framingham危险因素后，I型IFN与狼疮患者动脉粥样硬化的发展独立相关。本研究进一步支持I型干扰素促进系统性红斑狼疮早期血管损伤的假说。
Systemic lupus erythematosus (SLE) patients have a striking increase in cardiovascular (CV) comorbidity not fully explained by the Framingham risk score. Recent evidence from in vitro studies suggests that type I interferons (IFN) could promote premature CV disease (CVD) in SLE. We assessed the association of type I IFN signatures with functional and anatomical evidence of vascular damage, and with biomarkers of CV risk in a cohort of lupus patients without overt CVD. Serum type I IFN activity (induction of five IFN-inducible genes; IFIGs) from 95 SLE patient and 38 controls was quantified by real-time PCR. Flow mediated dilatation (FMD) of the brachial artery and carotid intima media thickness (CIMT) were quantified by ultrasound, and coronary calcification by computed tomography. Serum vascular biomarkers were measured by ELISA. We evaluated the effect of type I IFNs on FMD, CIMT and coronary calcification by first applying principal components analysis to combine data from five IFIGs into summary components that could be simultaneously modeled. Three components were derived explaining 97.1% of the total IFIG variation. Multivariable linear regression was utilized to investigate the association between the three components and other covariates, with the outcomes of FMD and CIMT; zero-inflated Poisson regression was used for modeling of coronary calcification. After controlling for traditional CV risk factors, enhanced serum IFN activity was significantly associated with decreased endothelial function in SLE patients and controls (p<0.05 for component 3), increased CIMT among SLE patients (p<0.01 for components 1 and 2), and severity of coronary calcification among SLE patients (p<0.001 for component 3). Type I IFNs are independently associated with atherosclerosis development in lupus patients without history of overt CVD and after controlling for Framingham risk factors. This study further supports the hypothesis that type I IFNs promote premature vascular damage in SLE.
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影响因子：
5.9
作者：
Mercuri, M;Bond, G;Ventura, A
通讯作者：
Ventura, A
影响因子：
8
作者：
Levy, Zohar;Rachmani, Rita;Harats, Dror
通讯作者：
Harats, Dror
影响因子：
5.9
作者：
HOSENPUD, JD;MONTANARO, A;KLOSTER, FE
通讯作者：
KLOSTER, FE
DOI：
10.1016/0735-1097(90)90282-t
发表时间：
1990-03-15
影响因子：
24
作者：
AGATSTON, AS;JANOWITZ, WR;DETRANO, R
通讯作者：
DETRANO, R
影响因子：
37.8
作者：
Grisar, J;Aletaha, D;Smolen, JS
通讯作者：
Smolen, JS