n-3 PUFA in CVD: influence of cytokine polymorphism
1Preventive Cardiology, Medizinische Klinik und Poliklinik Innenstadt, University of Munich, Ziemssenstrasse 1, D-80336 München, Germany. Clemens.vonschacky@med.uni-muenchen.de
Insights
Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular events by decreasing inflammation and oxidative stress. Dietary intake of EPA and DHA can alter gene expression, offering a novel approach to cardiovascular disease prevention.
Area of Science:
- Cardiovascular research
- Nutritional science
- Molecular biology
Background:
- Cardiac societies recommend eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for preventing cardiovascular complications.
- Atherosclerosis, an inflammatory disorder, is mitigated by EPA and DHA through antiarrhythmic and plaque-stabilizing effects.
Purpose of the Study:
- To investigate the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context through human dietary intervention studies.
- To explore how EPA and DHA influence pro-inflammatory cytokines, adhesion molecules, and oxidative stress markers.
Main Methods:
- Human dietary intervention studies assessing the impact of EPA and DHA consumption.
- Measurement of various pro-inflammatory cytokines (e.g., IL-1beta, IL-6, TNFalpha), adhesion molecules (e.g., ICAM-1, VCAM-1), and oxidative stress markers (e.g., F(2) isoprostane).
- Analysis of gene expression changes related to specific inflammatory markers like PDGF and MCP-1.
Main Results:
- Ingestion of EPA and DHA reduced levels of pro-inflammatory cytokines such as IL-1beta, IL-2, IL-6, TNFalpha, PDGF-A/B, and MCP-1 in human subjects.
- C-reactive protein levels remained largely unaltered, while soluble adhesion molecules showed reduction in some models.
- Urinary F(2) isoprostane excretion indicated a reduction in oxidative stress, contrary to expectations. Gene expression analysis revealed quantitative changes for PDGF and MCP-1.
Conclusions:
- Dietary EPA and DHA exert anti-inflammatory and antioxidant effects relevant to cardiovascular health.
- EPA and DHA intake can lead to significant alterations in gene expression, highlighting a direct molecular impact of diet.
- While mechanisms involving PPAR, NF-kappaB, and the eicosanoid system are suggested, further research is needed to fully elucidate how EPA and DHA modulate cytokine levels and inflammatory pathways.
Abstract:
In their current guidelines cardiac societies recommend the consumption of the two n-3 fatty acids EPA and DHA to prevent cardiovascular complications. Cardiovascular events are reduced by EPA and DHA, because they are antiarrhythmic, mitigate the course of atherosclerosis and stabilise plaque. As atherosclerosis is considered an inflammatory disorder a number of studies have investigated the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context in human dietary intervention studies. Pro-inflammatory cytokines, or cytokines reflecting inflammatory processes, e.g. IL-1beta, IL-2, IL-6, TNFalpha, platelet-derived growth factor (PDGF)-A and -B and monocyte chemoattractant protein-1 (MCP-1), are reduced by ingestion of EPA and DHA by human subjects. Interestingly, C-reactive protein remains largely unaltered. However, in in vitro and animal models, but less so in human subjects, soluble cytokines reflecting interactions between blood cells and the vessel wall, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, are reduced. Moreover, in contrast to common expectations, oxidative stress seems to be reduced after ingestion of EPA and DHA, at least as indicated by measurement of urinary F(2) isoprostane excretion. Notably, for PDGF-A and -B and for MCP-1 the reduction has been demonstrated to occur at the gene expression level, which indicates that a deliberate change in diet can alter gene expression quantitatively. The precise underlying mechanism, however, remains to be clarified, but might involve PPAR, NF-kappaB and/or the eicosanoid system. The same holds true for the mechanisms by which levels of other cytokines are altered by EPA and DHA.
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