Serum From Patients With Severe Heart Failure Downregulates eNOS and Is Proapoptotic

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.