TY - JOUR
T1 - Vasoactive factors in sickle cell disease
T2 - In vitro evidence for endothelin-1-mediated vasoconstriction
AU - Ergul, Sitki
AU - Brunson, Chris Y.
AU - Hutchinson, Jim
AU - Tawfik, Amany
AU - Kutlar, Abdullah
AU - Webb, R. Clinton
AU - Ergul, Adviye
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/7
Y1 - 2004/7
N2 - While systemic plasma endothelin-1 (ET-1) levels are increased during acute crisis in sickle cell disease, the relative levels of potent vasoactive factors that contribute to the regulation of vascular function, such as ET-1, NO, and cell-free hemoglobin, during the course of periodic vaso-occlusive episodes remain unclear. Moreover, whether and to what extent sickling-induced release of ET-1 alters vascular tone is not completely understood. To investigate the sequential changes in circulating vasoactive factors, we measured plasma ET-1, NO metabolites (NOx), and cell-free hemoglobin (Hb) before (steady-state), during (crisis), and after a vaso-occlusive (post-crisis) episode. Steady-state ET-1 levels (fmol/mL) increased from 2.3 ± 0.4 to 11.0 ± 1.4 and 4.2 ± 1.0 during crisis and post-crisis periods, respectively. There was no significant difference in plasma NOx levels. Cell-free Hb levels were significantly higher in sickle cell patients in all phases as compared to the control group, and especially during crisis cell-free Hb levels were elevated by 4-fold (209,000 ± 31,000 vs. 46,000 ± 5,300 ng/mL in steady-state). Conditioned medium from human pulmonary artery endothelial cells exposed to sickled erythrocytes prepared by deoxygenation induced contraction of aortic rings, and this effect was blocked by an ETA receptor antagonist. These findings indicate that ET-1 is the predominant contractile factor released by cultured endothelial cells upon exposure to deoxygenated sickled SS erythrocytes and ET-1-NO-NO scavenger balance is altered in favor of vasoconstriction during an acute episode in SCD.
AB - While systemic plasma endothelin-1 (ET-1) levels are increased during acute crisis in sickle cell disease, the relative levels of potent vasoactive factors that contribute to the regulation of vascular function, such as ET-1, NO, and cell-free hemoglobin, during the course of periodic vaso-occlusive episodes remain unclear. Moreover, whether and to what extent sickling-induced release of ET-1 alters vascular tone is not completely understood. To investigate the sequential changes in circulating vasoactive factors, we measured plasma ET-1, NO metabolites (NOx), and cell-free hemoglobin (Hb) before (steady-state), during (crisis), and after a vaso-occlusive (post-crisis) episode. Steady-state ET-1 levels (fmol/mL) increased from 2.3 ± 0.4 to 11.0 ± 1.4 and 4.2 ± 1.0 during crisis and post-crisis periods, respectively. There was no significant difference in plasma NOx levels. Cell-free Hb levels were significantly higher in sickle cell patients in all phases as compared to the control group, and especially during crisis cell-free Hb levels were elevated by 4-fold (209,000 ± 31,000 vs. 46,000 ± 5,300 ng/mL in steady-state). Conditioned medium from human pulmonary artery endothelial cells exposed to sickled erythrocytes prepared by deoxygenation induced contraction of aortic rings, and this effect was blocked by an ETA receptor antagonist. These findings indicate that ET-1 is the predominant contractile factor released by cultured endothelial cells upon exposure to deoxygenated sickled SS erythrocytes and ET-1-NO-NO scavenger balance is altered in favor of vasoconstriction during an acute episode in SCD.
KW - Endothelin-1
KW - Sickle cell disease
KW - Vasoactive factors
KW - Vasoconstriction
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U2 - 10.1002/ajh.20107
DO - 10.1002/ajh.20107
M3 - Article
C2 - 15224360
AN - SCOPUS:3042553343
SN - 0361-8609
VL - 76
SP - 245
EP - 251
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 3
ER -