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Spontaneous endothelin production by circulating mononuclear cells from patients with chronic heart failure but not
Insights
Mononuclear cells (MNC) in chronic heart failure (CHF) patients produce endothelin-1 (ET-1). This heightened ET-1 production by MNC may contribute to elevated plasma ET-1 levels observed in CHF.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Molecular Biology
Background:
- Plasma endothelin-1 (ET-1) levels are elevated in chronic heart failure (CHF).
- Chronic immunologic activation is a feature of CHF.
- Mononuclear cells (MNC) possess the capability to produce ET-1.
Purpose of the Study:
- To investigate the contribution of circulating MNC to increased plasma ET-1 levels in CHF patients.
- To determine if MNC from CHF patients produce ET-1 spontaneously or upon stimulation.
- To compare ET-1 production in MNC from CHF patients versus healthy individuals.
Main Methods:
- Collected MNC from eight CHF patients and six normal subjects.
- Assessed spontaneous ET-1 production by unseparated MNC, separated monocytes, and lymphocytes.
- Evaluated ET-1 production by CHF monocytes after macrophage colony-stimulating factor (MCSF) stimulation.
Main Results:
- Unseparated MNC from CHF patients spontaneously produced ET-1.
- CHF lymphocytes spontaneously produced ET-1, and CHF monocytes produced ET-1 after MCSF stimulation.
- No ET-1 production was observed in MNC from normal subjects, either spontaneously or after MCSF stimulation.
Conclusions:
- Heightened ET-1 production by MNC contributes to elevated plasma ET-1 levels in CHF patients.
- Contact between monocyte and lymphocyte subtypes within MNC may be essential for maximal ET-1 production in CHF.
Abstract:
1. Plasma endothelin-1 (ET-1) levels are increased in chronic heart failure (CHF). Because chronic immunologic activation occurs in CHF and mononuclear cells (MNC) are capable of ET-1 production, the possible contribution of circulating MNC to the increased plasma ET-1 levels in CHF patients was investigated. 2. Unseparated MNC (10(7)/mL) from eight CHF patients spontaneously produced ET-1 (1.54 +/- 0.37 pg/100 mL). After separation of MNC into monocytes (10(6)/mL) and lymphocytes (10(7)/mL) at ratios approximating those in the circulationg, ET-1 was spontaneously produced by CHF lymphocytes (0.81 +/- 0.26 pg/100 mL), and after macrophage colony stimulating factor (MCSF) stimulation by CHF monocytes (0.56 +/- 0.08 pg/100 mL). In contrast, there was neither spontaneous nor MCSF-induced production of ET-1 in six normal subjects. 3. It was concluded that heightened ET-1 production by MNC may contribute to increased plasma levels in CHF patients. Because unseparated MNC produced greater ET-1 than lymphocytes and monocytes separately, contact between these MNC subtypes may be necessary for maximal ET-1 production.