Spontaneous Endothelin Production by Circulating Mononuclear Cells From Patients With Chronic Heart Failure but Not From Normal Subjects

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.

Source of Endothelin-1 in Subarachnoid Hemorraghe

“…These data are consistent with previous in vitro work which demonstrated leukocytes to produce ET-1 (26)(27)(28)(29). Aging of blood coincubated with CSF stimulated leukocytes to synthesize ET-1.…”

Prognostic Value of Hemodynamic vs Big Endothelin Measurements During Long-term IV Therapy in Advanced Heart Failure Patients

“…The abnormally high big endothelin levels reported here could be the result of multiple mechanisms operative in patients with advanced left ventricular dysfunction, such as angiotensin II, norepinephrine, tumor necrosis factor-␣, or hypoxia occurring at multiple sites, including the large pulmonary endothelial surface or in circulating mononuclear cells. [17][18][19][20][21] Improved left ventricular loading conditions and a better hemodynamic profile resulting from continuous IV treatment are probably the major mechanisms for lowering big endothelin plasma levels that were found in the present study, which presumably occurred as a result of blunting some of the above-mentioned stimuli. 22,23…”