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Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human
1University of Oslo, The National Hospital, Ullevål Hospital Oslo, Norway. h.g.eiken@klinmed.uio.no
Insights
Interleukin-6 (IL-6) family cytokines, including leukaemia inhibitory factor (LIF), are present in human heart tissue. Elevated LIF mRNA in heart failure patients suggests its role in congestive heart failure (CHF) pathogenesis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Medicine
Background:
- Interleukin-6 (IL-6) cytokine family involvement suggested in congestive heart failure (CHF) pathogenesis.
- Previous studies utilized animal models and human plasma analyses.
- This study investigates IL-6-related cytokines in human chronic CHF myocardium.
Purpose of the Study:
- To examine gene and protein expression of IL-6-related cytokines in human chronic CHF.
- To analyze myocardial tissue from end-stage heart failure patients and donor hearts.
Main Methods:
- Gene expression analysis using cDNA array hybridization and RNase protection assays.
- Immunohistochemistry to detect leukaemia inhibitory factor (LIF), IL-6, and glycoprotein 130 (gp130).
- Analysis of myocardial samples from CHF patients and donor hearts.
Main Results:
- Majority of IL-6 family cytokines and receptors showed myocardial gene activity.
- IL-6, LIF, and gp130 localized to myocytes and vascular smooth muscle cells.
- Significantly elevated LIF mRNA in CHF patient left ventricles compared to donors (P < 0.005).
Conclusions:
- gp130 and its ligands IL-6 and LIF are expressed in both failing and non-failing human myocardium.
- Elevated LIF mRNA in end-stage CHF hearts suggests a role in CHF pathogenesis.
- Further research into LIF's role in heart failure is warranted.
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 gp130 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 gp130 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.
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