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Elevated circulating levels of C-C chemokines in patients with congestive heart failure
P Aukrust1, T Ueland, F Müller
1Research Institute for Internal Medicine, Medical Department A, University of Oslo, Rikshospitalet, Norway. pal.aukrust@klinmed.uio.no
Insights
Congestive heart failure (CHF) patients show elevated C-C chemokine levels, including macrophage chemoattractant protein-1 (MCP-1), indicating their role in heart failure pathogenesis. These elevated chemokines correlate with disease severity and monocyte activation.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Immunologic and inflammatory responses are implicated in congestive heart failure (CHF) pathogenesis.
- Leukocyte activation and migration are key components of these immune responses.
- C-C chemokines attract monocytes and lymphocytes, influencing their function.
Purpose of the Study:
- To measure circulating levels of three C-C chemokines in patients with CHF.
- To investigate the relationship between C-C chemokine levels and CHF severity.
- To explore the cellular sources and functional implications of elevated C-C chemokines in CHF.
Main Methods:
- Enzyme immunoassays were used to quantify macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and RANTES.
- 44 CHF patients and 21 healthy controls were analyzed.
- Monocyte activity and reactive oxygen species generation were assessed.
Main Results:
- CHF patients exhibited significantly higher levels of MCP-1, MIP-1alpha, and RANTES compared to controls.
- Elevated chemokine levels, particularly MCP-1, were associated with higher New York Heart Association class and lower left ventricular ejection fraction.
- Platelets, lymphocytes, and monocytes were identified as potential contributors to increased C-C chemokine levels in CHF.
Conclusions:
- Increased circulating C-C chemokine levels are a novel finding in CHF.
- These chemokines may represent previously unrecognized pathogenic factors in the development and progression of CHF.
- Elevated MCP-1 levels correlate with increased monocyte activity and may contribute to CHF pathophysiology.
Background:
Immunologic and inflammatory responses appear to play a pathogenic role in the development of congestive heart failure (CHF). Activation and migration of leukocytes to areas of inflammation are important factors in these immunologic responses. Because the C-C chemokines are potent chemoattractants of monocytes and lymphocytes and can modulate other functions of these cells (eg, generation of reactive oxygen species), we measured circulating levels of three C-C chemokines in CHF.
Methods And Results:
Levels of macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein- 1alpha (MIP-1alpha), and RANTES (regulated on activation normally T-cell expressed and secreted) were measured by enzyme immunoassays in 44 patients with CHF and 21 healthy control subjects. CHF patients had significantly elevated levels of all chemokines with the highest levels in New York Heart Association class IV, and MCP-1 and MIP-1alpha levels were significantly inversely correlated with left ventricular ejection fraction. Elevated C-C chemokine levels were found independent of the cause of the heart failure, but MCP-1 levels were particularly raised in patients with coronary artery disease. Studies on cells isolated from peripheral blood suggested that platelets, CD3+ lymphocytes, and in particular, monocytes, might contribute to the elevated C-C chemokine levels in CHF. The increased MCP-1 levels in CHF were correlated with increased monocyte activity reflected in an enhancing effect of serum from CHF patients on O2-generation in monocytes, which was inhibited by neutralizing antibodies against MCP-1.
Conclusions:
This first demonstration of increased circulating levels of C-C chemokines in CHF with particularly high levels in patients with severe disease may represent previously unrecognized pathogenic factors in CHF.