Endothelial cell activation in patients with decompensated heart failure

Circulation. 2005 Jan 4;111(1):58-62. doi: 10.1161/01.CIR.0000151611.89232.3B. Epub 2004 Dec 20.


Background: Vascular endothelial functions, other than nitric oxide (NO)-mediated control of vasomotor tone, are poorly characterized in patients with chronic heart failure (CHF). Veins and arteries are exposed to the same circulating proinflammatory mediators in patients with CHF. The present study tested whether endothelial cell activation occurs in veins of patients with decompensated CHF and whether activation, if present, subsides with return to a clinically compensated state.

Methods and results: Fifteen patients with decompensated CHF requiring transient inotropic support and 6 age-matched, healthy controls were studied. Endothelial cells and blood were collected from a forearm vein, and brachial artery flow-mediated dilation (FMD) was measured before and 24 hours after discontinuation of short-term inotropic therapy, when patients had returned to a steady compensated state. Nitrotyrosine immunoreactivity (an intracellular marker of oxidative stress), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) expression were significantly higher in venous endothelial cells of patients in clinical decompensation when compared with healthy subjects. Return to a compensated state resulted in a significant reduction in nitrotyrosine immunoreactivity, COX-2, and iNOS expression. Concomitantly, a significant increase in FMD and a decline in plasma total 8-isoprostane and bicycloprostaglandin E2 levels were observed. Venous endothelial NOS expression was unaffected by clinical decompensation.

Conclusions: Clinical decompensation in CHF is associated with activation of the venous endothelium. Return to a compensated state after short-term inotropic therapy results in a significant reduction in endothelial nitrotyrosine formation, COX-2, and iNOS expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Brachial Artery / physiopathology
  • Cardiotonic Agents / therapeutic use
  • Cells, Cultured / drug effects
  • Cyclooxygenase 2
  • Dinoprost / analogs & derivatives*
  • Dinoprost / blood
  • Dinoprostone / analogs & derivatives*
  • Dinoprostone / blood
  • Endothelium, Vascular / physiopathology*
  • Enzyme Induction
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology*
  • Humans
  • Male
  • Membrane Proteins
  • Middle Aged
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Oxidative Stress
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Tyrosine / analogs & derivatives*
  • Tyrosine / analysis
  • Vasodilation
  • Veins / enzymology
  • Veins / physiopathology


  • Cardiotonic Agents
  • Membrane Proteins
  • 8-epi-prostaglandin F2alpha
  • 3-nitrotyrosine
  • Tyrosine
  • 11-deoxy-15-keto-13,14-dihydro-11 beta,16-cycloprostaglandin E2
  • Dinoprost
  • NOS2 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone