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

Abstract

SummaryEndothelial 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.

Cardiac involvement in sickle β-thalassemia

“…Both endothelial dysfunction and increased arterial stiffness have been encountered in β-thalassemia, SCD, and S-Thal patients [7,27,28] while arterial hypertension was encountered in nearly 8% of our patients. Given also the high-output state, it is obvious that the left ventricle is in a continuous state of both volume and pressure overload.…”

Non-Conventional Pain Management for Sickle Cell Disease

“…Anti-coagulant treatment: Treatment with heparin, has been considered as an additional therapeutic approach to block sickle cell adhesion to endothelial cells through the P-selectin pathway [96], or binding to TSP that can mediate the interactions between sickle erythrocytes and the vascular endothelial surface. A doubleblind randomized trial with tinzaparin in SCD patients during acute vaso-occlusive events documented a reduction of their severity and duration [97].…”

Sodium phenyl butyrate downregulates endothelin‐1 expression in cultured human endothelial cells: Relevance to sickle‐cell disease

“…It is increased in SCD, particularly during vaso-occlusive crises [19,21] or acute chest syndrome [22], and reduced in HUtreated patients [23]. Levels of soluble endotheliumderived adhesion molecules in patients with SCD are associated with pulmonary hypertension, organ dysfunction and mortality [24]. ICAM-1 is an EC surface glycoprotein implicated in leukocyte adhesion.…”

“…VCAM-1 is the endothelial receptor for the very late activation antigen 4 (VLA-4) at the surface of sickle erythrocytes [27]. Its soluble form is increased in SCD patients and at least two studies suggest that it may be decreased by HU treatment [24,26].…”