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.
Methods and 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.