Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality

Gregory J. Kato, Sabrina Martyr, William C. Blackwelder, James S. Nichols, Wynona A. Coles, Lori A. Hunter, Marie Luise Brennan, Stanley L. Hazen, Mark T. Gladwin

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelial cell adhesion molecules orchestrate the recruitment and binding of inflammatory cells to vascular endothelium. With endothelial dysfunction and vascular injury, the levels of endothelial bound and soluble adhesion molecules increase. Such expression is modulated by nitric oxide (NO), and in patients with sickle cell disease (SCD), these levels are inversely associated with measures of NO bioavailability. To further evaluate the role of endothelial dysfunction in a population study of SCD, we have measured the levels of soluble endothelium-derived adhesion molecules in the plasma specimens of 160 adult patients with SCD during steady state. Consistent with a link between endothelial dysfunction and end-organ disease, we found that higher levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were associated with markers indicating renal dysfunction and hepatic impairment. Analysis of soluble intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin and sP-selectin levels indicated partially overlapping associations with sVCAM-1, with an additional association with inflammatory stress and triglyceride levels. Importantly, increased soluble adhesion molecule expression correlated with severity of pulmonary hypertension, a clinical manifestation of endothelial dysfunction. Soluble VCAM-1, ICAM-1, and E-selectin were independently associated with the risk of mortality in this cohort. Our data are consistent with steady state levels of soluble adhesion molecules as markers of pulmonary hypertension and risk of death.

Original languageEnglish (US)
Pages (from-to)943-953
Number of pages11
JournalBritish journal of haematology
Volume130
Issue number6
DOIs
StatePublished - Sep 2005

Keywords

  • Adhesion molecules
  • Endothelial function
  • Liver disease
  • Sickle cell disease
  • Vascular biology

ASJC Scopus subject areas

  • Hematology

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