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Tumour necrosis factor is expressed in cardiac tissues of patients with heart failure
K Doyama1, H Fujiwara, M Fukumoto
1Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Insights
Tumour necrosis factor (TNF) is present in human heart tissue, particularly in patients with severe congestive heart failure (CHF). This study demonstrates TNF production by cardiac myocytes and vascular cells in CHF patients.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Tumour necrosis factor (TNF), a cytokine primarily from macrophages, is implicated in cardiac diseases like congestive heart failure (CHF).
- Previous research noted elevated serum TNF in CHF, but its expression within human cardiac tissue remained unconfirmed.
Purpose of the Study:
- To investigate the presence and expression of TNF in human atrial tissue.
- To determine if TNF is produced by cardiac myocytes and vascular cells, and if its levels correlate with CHF severity.
Main Methods:
- Analysis of right atrial (RA) specimens from 15 cardiac surgery patients.
- Utilized immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR) to detect TNF and its mRNA.
Main Results:
- TNF immunoreactivity was detected in cardiac myocytes and vascular smooth muscle cells of patients with severe CHF, but not in those without severe CHF.
- ELISA confirmed higher TNF levels in RA tissues from severe CHF patients compared to controls.
- RT-PCR detected TNF mRNA in all examined atrial tissue samples, indicating TNF gene expression.
Conclusions:
- Atrial tissue expresses TNF mRNA.
- The production of TNF peptides by cardiac myocytes and vascular smooth muscle cells is increased in patients with severe CHF, suggesting a role in the disease pathology.
Abstract:
Tumour necrosis factor (TNF), a cytokine produced mainly by macrophages, has also been found in vascular smooth muscle cells. Elevated serum levels of TNF have been reported in various cardiac diseases, especially congestive heart failure (CHF). Although the myocardium produces several cytokines, the expression of TNF in human cardiac tissue has not yet been demonstrated. We examined TNF expression in right atrial (RA) specimens obtained from 15 patients during cardiac surgery with immunohistochemistry using an anti-human TNF monoclonal antibody, enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). TNF immunoreactivity was found only in cardiac myocytes and some vascular smooth muscle cells of small vessels of specimens from patients with severe CHF (3/5), and not in those from patients without severe CHF (0/10). ELISA of four RA specimens revealed that RA tissues from two patients with severe CHF contained more TNF than did those from two patients without severe CHF (3.1 and 4.7 pg/mg vs. 0.1 and 0.3 pg/mg). RT-PCR revealed TNF mRNA in all seven cases we examined. It was concluded that TNF mRNA is expressed by atrial tissue. The production of immunoreactive TNF-like peptides by myocytes and vascular smooth muscle cells is augmented in patients with severe CHF.