title: Activation of endothelial cells in conduit veins of dogs with heart failure and veins of normal dogs after vascular stretch by acute volume loading.
abstract: BACKGROUND
  The venous endothelium is a key regulator of central blood volume, organ perfusion, and hemostasis in heart failure (HF). We previously reported activation of the inflammatory/oxidative program in venous endothelial cells collected from decompensated HF patients. The underlying causes are unknown. We tested the hypothesis that the pro-inflammatory state of HF and vascular strain associated with congestion can activate the endothelial inflammatory/oxidative and hemostatic programs.
  
  
  RESULTS
  We studied 6 normal (NL) dogs (left ventricular ejection fraction [LVEF] >50%, central venous pressure [CVP] = 8 +/- 2 mm Hg) and 6 dogs with HF (LVEF approximately 30%, CVP 8 +/- 2 mm Hg) produced by intracoronary microembolizations. Normal dogs were studied at baseline and 1 hour after fluid load to a target CVP >or=20 mm Hg. Endothelial cells were scraped from jugular veins; mRNA expression was analyzed by reverse transcription polymerase chain reaction. The endothelial inflammatory/oxidative and hemostatic programs were significantly activated in HF dogs compared with NL. In NL dogs, fluid load significantly activated the endothelial inflammatory/oxidative and hemostatic programs, and, concurrently, caused a significant increase in plasma neurohumoral indices to levels that approached those of HF dogs.
  
  
  CONCLUSIONS
  The pro-inflammatory state of HF and vascular strain associated with congestion can both activate venous endothelial cells in dogs in a manner consistent with that seen in HF patients.
authors.affiliation: Department of Medicine, Division of Cardiology, New York Presbyterian Hospital, Columbia University College of Physicians & Surgeons, New York, New York, USA.
authors.forename: Paolo C
authors.initials: PC
authors.lastname: Colombo
authors.forename: Sharad
authors.initials: S
authors.lastname: Rastogi
authors.forename: Duygu
authors.initials: D
authors.lastname: Onat
authors.forename: Valerio
authors.initials: V
authors.lastname: Zacà
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Ulrich P
authors.initials: UP
authors.lastname: Jorde
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D042783:Endothelial Cells / Q000502:physiology*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007601:Jugular Veins / Q000473:pathology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D013318:Stroke Volume; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
chemical_list: D019332:Endothelin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012313:RNA