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-alpha (TNF-alpha) 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 [P<0.05] and 48 hours [P<0.001]), (2) nuclear morphological changes typical of apoptosis; and (3) a high apoptotic rate with propidium iodide (increasing from 2.1+/-0.4% to 11.3+/-1.2% at 48 hours; P<0.001 versus healthy subjects) and annexin V. An anti-human TNF-alpha antibody did not completely counteract these effects. A strong correlation existed between eNOS downregulation and apoptosis (r = -0.89; P<0.001). CONCLUSIONS: Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-alpha likely play a role, but they cannot be the only factor responsible.
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-alpha (TNF-alpha) 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 [P<0.05] and 48 hours [P<0.001]), (2) nuclear morphological changes typical of apoptosis; and (3) a high apoptotic rate with propidium iodide (increasing from 2.1+/-0.4% to 11.3+/-1.2% at 48 hours; P<0.001 versus healthy subjects) and annexin V. An anti-humanTNF-alpha antibody did not completely counteract these effects. A strong correlation existed between eNOS downregulation and apoptosis (r = -0.89; P<0.001). CONCLUSIONS: Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-alpha likely play a role, but they cannot be the only factor responsible.
Authors: Ramazan Gökmen Turan; Ilkay Bozdag-Turan; Jasmin Ortak; Ibrahim Akin; Stephan Kische; Henrik Schneider; Cem Hakan Turan; Tim Christopher Rehders; Mathias Rauchhaus; Tilo Kleinfeldt; Ester Adolph; Micheal Brehm; Sedat Yokus; Stephan Steiner; Kurtulus Sahin; Christoph A Nienaber; Hüseyin Ince Journal: Stem Cells Dev Date: 2010-12-29 Impact factor: 3.272
Authors: Arne Yndestad; Jan Kristian Damås; Erik Oie; Thor Ueland; Lars Gullestad; Pål Aukrust Journal: Heart Fail Rev Date: 2006-03 Impact factor: 4.214
Authors: Mihai Gheorghiade; Catherine N Marti; Hani N Sabbah; Lothar Roessig; Stephen J Greene; Michael Böhm; John C Burnett; Umberto Campia; John G F Cleland; Sean P Collins; Gregg C Fonarow; Phillip D Levy; Marco Metra; Bertram Pitt; Piotr Ponikowski; Naoki Sato; Adriaan A Voors; Johannes-Peter Stasch; Javed Butler Journal: Heart Fail Rev Date: 2013-03 Impact factor: 4.214
Authors: Steven P Jones; James J M Greer; Rien van Haperen; Dirk J Duncker; Rini de Crom; David J Lefer Journal: Proc Natl Acad Sci U S A Date: 2003-04-03 Impact factor: 11.205
Authors: Károly Palatka; Zoltán Serfozo; Zoltán Veréb; Róbert Bátori; Beáta Lontay; Zoltán Hargitay; Zoltán Nemes; Miklós Udvardy; Ferenc Erdodi; István Altorjay Journal: World J Gastroenterol Date: 2006-03-21 Impact factor: 5.742