Abstract 14828: Comparison of Expression Profiling of the Vascular Endothelium in Patients With Heart Failure and in Healthy Subjects Using a Novel Methodology: Human Endothelial Sampling Coupled With Microarray Analysis

Background: In heart failure (HF), veins are chronically exposed to higher levels of endovascular pressure and of circulating pro-inflammatory mediators, which might contribute to a modified endothelial cell (EC) phenotype. We studied gene expression signatures in venous ECs collected from HF patients and compared to those from healthy subjects to gain insights into the pathobiology of the venous endothelium in HF patients. Methods: 29 symptomatic (NYHA Class II-III) out-patients with compensated HF (28% female, aged 50±12 years) and 16 healthy subjects (31% female, aged 38±9 years) were studied. ECs were collected from arm veins using endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 Plus 2.0 Microarray. mRNA data were normalized and differential gene expression between HF patients and controls was studied using generalized linear regression models. A false discovery rate (FDR) of 5% was used to determine statistical significance. Signaling Pathway Impact Analysis (SPIA) identified possible biological pathways impacted in the vascular endothelium of HF patients. Results: No adverse events were observed. Peripheral venous pressure in HF patients was 8±3mmHg vs. 5±2 mmHg in healthy subjects (p Conclusion: We provide the first comparison of venous EC gene expression between HF patients and healthy controls. A large number of genes and signaling pathways of possible relevance to HF were differentially expressed among HF patents. These data can help generate novel insights into the pathobiology of endothelial dysfunction in HF by identifying yet unrecognized biologic pathways for more focused study.