Abstract 1954: Activation of Endothelial Cells in Conduit Veins of Dogs With Heart Failure and Veins of Normal Dogs Following Vascular Stretch by Acute Volume Loading
Background: Endothelial dysfunction is an independent predictor of poor prognosis in patients with heart failure (HF). Using a novel approach of endovascular endothelial cell (EC) sampling, we previously showed that ECs collected from conduit veins using J-wires are activated in patients with HF as evidenced by increased expression of pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The underlying cause(s) of this endothelial activation and dysfunction is not known. In this study, we tested the hypothesis that the HF state itself and the vascular strain associated with congestion can both account for these findings.
Methods: We studied 6 normal (NL) dogs (LV ejection fraction >50%, central venous pressure (CVP) ~ 8 mmHg) and 6 dogs with HF (ejection fraction ~ 30%, CVP ~9 mmHg) produced by intracoronary microembolizations. This model of HF manifests the disease syndrome in the absence of other co-morbid conditions often present in patients with CHF. NL dogs were studied at baseline and 1 hr after rapid fluid load (500 ml Dextran-40) resulting in CVP>20 mmHg. ECs were scraped from jugular veins. mRNA was analyzed by RT-PCR and quantified in densitometric units (du).
Results: Data are shown in the table⇓. Endothelial iNOS and COX-2 were increased in HF dogs compared to NL. Tissue necrosis factor (TNF)-α, early growth response gene (EGR-1), receptor for advanced glycation end products (RAGE) and glutathione peroxidase (GPx) were also up-regulated in HF. In NL dogs, fluid load increased iNOS, COX-2, TNF-α, Egr-1, RAGE and GPx to levels that approached those of HF.
Conclusions: The HF state itself, in the absence of other co-morbid conditions, and vascular stretch are both sufficient to activate venous ECs in dogs in a manner consistent with that seen in patients with HF. As such, molecular measures of EC dysfunction may potentially serve as “biomarkers” of severity of HF and possibly of impending decompensation.