Activation of endothelial cells in conduit veins of dogs with heart failure and veins of normal dogs after vascular stretch by acute volume loading.
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.
Colombo
Paolo C
PC
Department of Medicine, Division of Cardiology, New York Presbyterian Hospital, Columbia University College of Physicians & Surgeons, New York, New York, USA.
Rastogi
Sharad
S
Onat
Duygu
D
Zacà
Valerio
V
Gupta
Ramesh C
RC
Jorde
Ulrich P
UP
Sabbah
Hani N
HN
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*
D019332:Endothelin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012313:RNA