Serum From Patients With Severe Heart Failure Downregulates eNOS and Is Proapoptotic
- 9 November 1999
- journal article
- other
- Published by Wolters Kluwer Health in Circulation
- Vol. 100 (19) , 1983-1991
- https://doi.org/10.1161/01.cir.100.19.1983
Abstract
Background—Cytokine activation and endothelial dysfunction are typical phenomena of congestive heart failure (CHF). We tested the hypothesis that incubating human umbilical vein endothelial cells with serum from patients with CHF will downregulate endothelial constitutive nitric oxide synthase (eNOS) and induce apoptosis. Methods and Results—We studied 21 patients with severe CHF. Levels of tumor necrosis factor-α (TNF-α) and several neuroendocrine parameters were assessed. eNOS was measured by Western Blot analysis and apoptosis by optical microscopy and flow cytometry. We observed (1) eNOS downregulation (difference versus healthy subjects at 24 hours [PPPr=−0.89; PConclusions—Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-α likely play a role, but they cannot be the only factor responsible.Keywords
This publication has 19 references indexed in Scilit:
- Apoptosis by Death FactorCell, 1997
- Tumor necrosis factor-α and the failing human heart-TNFα and heart failureClinical Cardiology, 1995
- A novel assay for apoptosis Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin VJournal of Immunological Methods, 1995
- Essential genes that regulate apoptosisTrends in Cell Biology, 1994
- Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity.Journal of Clinical Investigation, 1994
- Two TNF receptorsImmunology Today, 1992
- PROGRAMMED CELL DEATH: CONCEPT, MECHANISM AND CONTROLBiological Reviews, 1992
- Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart FailureNew England Journal of Medicine, 1990
- Noradrenaline, atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive cardiac failureCardiovascular Research, 1989
- Culture of Human Endothelial Cells Derived from Umbilical Veins. IDENTIFICATION BY MORPHOLOGIC AND IMMUNOLOGIC CRITERIAJournal of Clinical Investigation, 1973