Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation

Paolo C. Colombo, Duygu Onat, Ante Harxhi, Ryan T. Demmer, Yacki Hayashi, Sanja Jelic, Thierry H. Lejemtel, Loredana Bucciarelli, Moritz Kebschull, Panos Papapanou, Nir Uriel, Ann Marie Schmidt, Hani N. Sabbah, Ulrich P. Jorde

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

AimsVolume 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.MethodsTo 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.ResultsPlasma 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.ConclusionPeripheral 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.

Original languageEnglish (US)
Pages (from-to)448-454
Number of pages7
JournalEuropean heart journal
Volume35
Issue number7
DOIs
StatePublished - Feb 2014
Externally publishedYes

Keywords

  • Congestive heart failure
  • Endothelin
  • Endothelium
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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