title: Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation.
abstract: OBJECTIVE
  Volume overload and venous congestion are typically viewed as a consequence of advanced and of acute heart failure (HF) and renal failure (RF) although it is possible that hypervolaemia itself might be a critical intermediate in the pathophysiology of these diseases. This study aimed at elucidating whether peripheral venous congestion is sufficient to promote changes in inflammatory, neurohormonal, and endothelial phenotype similar to those observed in HF and RF.
  
  
  METHODS
  To experimentally model peripheral venous congestion, we developed a new method (so-called venous stress test) and applied the methodology on 24 healthy subjects (14 men, age 35 ± 2 years). Venous arm pressure was increased to ∼30 mmHg above the baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 min of venous congestion, using angiocatheters and endovascular wires. Magnetic beads coated with EC-specific antibodies were used for EC separation; amplified mRNA was analysed by Affymetrix HG-U133 Plus 2.0 Microarray.
  
  
  RESULTS
  Plasma interleukin-6 (IL-6), endothelin-1 (ET-1), angiotensin II (AII), vascular cell adhesion molecule-1 (VCAM-1), and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. A total of 3437 mRNA probe sets were differentially expressed (P < 0.05) in venous ECs before vs. after testing, including ET-1, VCAM-1, and CXCL2.
  
  
  CONCLUSIONS
  Peripheral venous congestion causes release of inflammatory mediators, neurohormones, and activation of ECs. Overall, venous congestion mimicked, notable aspects of the phenotype typical of advanced and of acute HF and RF.
authors.affiliation: Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Paolo C
authors.initials: PC
authors.lastname: Colombo
authors.forename: Duygu
authors.initials: D
authors.lastname: Onat
authors.forename: Ante
authors.initials: A
authors.lastname: Harxhi
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demmer
authors.forename: Yacki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Sanja
authors.initials: S
authors.lastname: Jelic
authors.forename: Thierry H
authors.initials: TH
authors.lastname: LeJemtel
authors.forename: Loredana
authors.initials: L
authors.lastname: Bucciarelli
authors.forename: Moritz
authors.initials: M
authors.lastname: Kebschull
authors.forename: Panos
authors.initials: P
authors.lastname: Papapanou
authors.forename: Nir
authors.initials: N
authors.lastname: Uriel
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: Ulrich P
authors.initials: UP
authors.lastname: Jorde
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D001132:Arm / Q000098:blood supply; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014657:Vasculitis / Q000209:etiology*
chemical_list: D016207:Cytokines; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II
keywords: Congestive heart failure; Endothelin; Endothelium; Inflammation