Related Experiment Videos
Cytokines and cardiomyocyte death
1Department of Clinical Chemistry, University of Turku, Finland. kari.pulkki@utu.fi
Insights
Proinflammatory cytokines contribute to heart failure by inducing cardiomyocyte apoptosis. Understanding these pathways may lead to new therapies to prevent heart muscle cell loss.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Death Research
Background:
- Cytokines are implicated in acute coronary syndromes and chronic heart failure (CHF), conditions marked by cardiomyocyte loss.
- Elevated serum levels of proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and soluble TNF receptor are observed in CHF.
- TNF and Fas-ligand can induce cardiomyocyte apoptosis, a process exacerbated by ischemia.
Purpose of the Study:
- To review the role of cytokines in cardiomyocyte apoptosis.
- To explore potential therapeutic targets for preventing cytokine-induced cardiomyocyte loss.
Main Methods:
- Literature review of studies on cytokine involvement in heart failure and apoptosis.
- Analysis of experimental data on TNF, Fas-ligand, and nitric oxide effects on cardiomyocytes.
- Examination of the role of anti-inflammatory cytokines and growth hormone.
Main Results:
- Proinflammatory cytokines (IL-1, IL-2, interferon-gamma) can stimulate TNF production and nitric oxide release, impairing cardiac function and inducing apoptosis.
- Anti-inflammatory cytokines (IL-10, IL-4, IL-13) counteract proinflammatory cytokine production.
- Cardiotrophin-1 and growth hormone show potential in inhibiting cytokine-induced cardiomyocyte apoptosis.
Conclusions:
- Cytokine-mediated apoptosis is a significant factor in progressive cardiomyocyte loss in heart failure.
- Further understanding of cytokine-induced pathways in cardiomyocytes is crucial for developing novel therapeutic strategies.
- Targeting cytokine-induced apoptosis offers a promising avenue for preventing heart muscle cell death.
Abstract:
Cytokines have been associated with the pathogenesis of acute coronary syndromes and chronic heart failure (CHF), which are both associated with cardiomyocyte loss. In CHF, increased serum concentrations of proinflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha) and also soluble TNF receptor have been found. Both TNF and Fas-ligand have been able to induce programmed cell death (apoptosis) of cardiomyocytes in various experimental studies. In ischaemic conditions of the heart, increased serum levels of soluble Fas receptor have been found. The proinflammatory cytokines interleukin 1 (IL-1), IL-2 and interferon-gamma can induce TNF production from target cells, including myocytes. TNF and some other cytokines are able to induce nitric oxide production, which depresses cardiac function and can induce apoptosis. However, anti-inflammatory cytokines such as IL-10, IL-4 and IL-13, secreted by T-helper type 2 lymphocytes and other cells, inhibit the production of proinflammatory cytokines. Preliminary studies suggest that cardiotrophin-1, produced by cardiomyocytes, is able to inhibit cytokine-induced cardiomyocyte apoptosis in vitro. As growth hormone is able to inhibit the production of proinflammatory cytokines in many cell types, it may also play an important role in the regulation of apoptosis induced by these cytokines. When the cytokine-induced pathways leading to altered gene expression of cardiomyocytes are understood, this knowledge may aid in the development of drugs that prevent progressive cardiomyocyte loss, in particular by inhibiting cytokine-induced apoptosis.