Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury.

Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury.
复制标题

DOI:
10.1371/journal.pone.0012106
复制
发表时间:
2010-08-17
期刊:
影响因子:
3.7
通讯作者:
Lafyatis R
Lafyatis R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pendergrass SA;Hayes E;Farina G;Lemaire R;Farber HW;Whitfield ML;Lafyatis R

文献摘要

参考文献

被引文献

相似文献

肺动脉高压(PAH)是局限性系统性硬化症(lSSc)患者的常见并发症。lSSc-PAH生物标志物的鉴定和表征应导致侵入性更小的筛查,更好地理解发病机制和改善治疗。从21名无PAH的lSSc受试者(lSSc-noPAH)、15名患有PAH的lSSc受试者(lSSc-PAH)和10名健康对照者获得49份PBMC样品;三名受试者在一年后提供PBMC。测量每个样品的全基因组基因表达。通过多分析物分析(MAP)免疫测定法测量来自受试者子集的血清中89种细胞因子的水平。基因表达清楚地区分了lSSc样品与健康对照,并将lSSc-PAH与lSSc-NoPAH患者分开。实时定量PCR证实lSSc-PAH患者中9个基因(ICAM 1、IFNGR 1、IL 1B、IL 13 Ra 1、JAK 2、AIF 1、CCR 1、ALAS 2、TIMP 2)表达增加。在lSSc-PAH受试者中发现炎性介质(如TNF-α、IL 1-β、ICAM-1和IL-6)和血管损伤标志物(如VCAM-1、VEGF和血管性血友病因子)的循环细胞因子水平升高。lSSc-PAH患者的基因表达和细胞因子谱表明存在活化的单核细胞,并显示血管损伤和炎症的标志物。这些基因和因子可以作为PAH参与lSSc的生物标志物。
Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment. Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects. The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc.
DOI: 10.1016/j.trsl.2007.12.010
发表时间: 2008-04-01
影响因子: 7.8
作者:
Grigoryev, Dmitry N.;Mathai, Stephen C.;Hassoun, Paul M.
通讯作者: Hassoun, Paul M.
DOI: 10.1038/ni.1703
发表时间: 2009-03
期刊: Nature immunology
影响因子: 30.5
作者:
通讯作者: --
DOI: 10.1016/j.bbrc.2004.12.184
发表时间: 2005-03-11
影响因子: 3.1
作者:
Hirotani, T;Yamamoto, M;Akira, S
通讯作者: Akira, S
DOI: 10.1152/japplphysiol.00083.2002
发表时间: 2002-12-01
影响因子: 3.3
作者:
Fujita, M;Mason, RJ;Fagan, KA
通讯作者: Fagan, KA
DOI: 10.1080/17482940802409662
发表时间: 2008-01-01
期刊: Acute cardiac care
影响因子: --
作者:
Herlitz, J;Svensson, L
通讯作者: Svensson, L