Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure
Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure
复制标题
DOI：
10.1046/j.1365-2362.2001.00795.x
复制
发表时间：
2001-05-01
影响因子：
5.5
通讯作者：
Aukrust, P
中科院分区：
文献类型：
--
作者：
Eiken, HG;Oie, E;Aukrust, P
背景 对不同动物模型的研究和人类血浆分析表明，白细胞介素 6 (IL-6) 细胞因子家族的成员可能参与充血性心力衰竭 (CHF) 的发病机制。因此，我们通过分析终末期心力衰竭患者和供体心脏的心肌中的基因和蛋白质表达，检查了人类慢性CHF中IL-6相关的细胞因子。方法使用cDNA阵列杂交和RNase保护测定记录了心肌样本中IL-6家族细胞因子/受体的基因表达。采用免疫组织化学方法检测心肌组织中的白血病抑制因子（LIF）、IL-6和糖蛋白130（gp130）。结果记录了大多数IL-6家族细胞因子及其受体的心肌基因活性。免疫组织化学分析将 IL-6、LIF 及其共同受体亚基 gp 130 定位于肌细胞和血管平滑肌细胞。相对于供体心脏的左心室，CHF 患者左心室的 LIF mRNA 水平有所增强（患者 4.6 +/- 4.7 vs 供体 0.3 +/- 0.3，P < 0.005）。患者和供体之间的心肌IL-6和gp 130 mRNA水平没有统计学差异，但与心脏外植体中的LIF mRNA表达相比，患者和供体中左心房中的gp130 mRNA水平显着高于左心室。 结论 gp130及其配体IL-6和LIF的mRNA和蛋白在非衰竭和衰竭的人类心肌中均表达。终末期心力衰竭患者左心室中 LIF mRNA 水平升高表明 LIF 在 CHF 发病机制中发挥作用。
Background Studies in different animal models and plasma analyses in humans suggest that members of the interleukin-6 (IL-6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL-6-related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end-stage heart failure and donor hearts.Methods Gene expression of cytokines/receptors of the IL-6 family was documented in myocardial samples using cDNA array hybridization and RNase protection assays. Immunohistochemistry was used to detect leukaemia inhibitory factor (LIF), IL-6 and glycoprotein 130 (gp130) in myocardial tissues.Results Myocardial gene activity was documented for the majority of IL-6 family cytokines and their receptors. Immunohistochemical analysis localized IL-6, LIF and their common receptor subunit gp 130 to myocytes and vascular smooth muscle cells. LIF mRNA levels were enhanced in the left ventricles of CHF patients relative to the left ventricles of donor hearts (patients 4.6 +/- 4.7 vs. donors 0.3 +/- 0.3, P < 0.005). Myocardial IL-6 and gp 130 mRNA levels were not statistically different between patients and donors, but in contrast to LIF mRNA expression in heart explants, gp130 mRNA levels were significantly higher in left atrium compared with left ventricle in both patients and donors.Conclusions Both mRNA and proteins of gp130 and its ligands IL-6 and LIF are expressed in both nonfailing and failing human myocardium. The elevated LIF mRNA levels in left ventricles from patients with end-stage heart failure suggest a role for LIF in the pathogenesis of CHF.