Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity: Effects on Vascular Adhesion and Reactivity

Sandip K. Bains; Roberta Foresti; Jo Howard; Sangeeta Atwal; Colin J. Green; Roberto Motterlini

doi:10.1161/ATVBAHA.109.196360

Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity: Effects on Vascular Adhesion and Reactivity

Sandip K. Bains, Roberta Foresti^*, Jo Howard, Sangeeta Atwal, Colin J. Green, Roberto Motterlini

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

Abstract

Objective-Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD.

Methods and Results-We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas.

Conclusions-Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD. (Arterioscler Thromb Vasc Biol. 2010;30:305-312.)

Original language	English
Pages (from-to)	305-U331
Number of pages	13
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	30
Issue number	2
DOIs	https://doi.org/10.1161/ATVBAHA.109.196360
Publication status	Published - Feb 2010

Keywords

adhesion
carbon monoxide
endothelium
heme oxygenase
sickle cell disease
MONOXIDE-RELEASING MOLECULES
CARBON-MONOXIDE
OXIDATIVE-STRESS
GENE-EXPRESSION
NITRIC-OXIDE
DISEASE
VASOOCCLUSION
INFLAMMATION
MECHANISMS
INDUCTION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/ATVBAHA.109.196360

Cite this

@article{88d3077251114a55a2061d3e4150f917,

title = "Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity: Effects on Vascular Adhesion and Reactivity",

abstract = "Objective-Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD.Methods and Results-We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas.Conclusions-Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD. (Arterioscler Thromb Vasc Biol. 2010;30:305-312.)",

keywords = "adhesion, carbon monoxide, endothelium, heme oxygenase, sickle cell disease, MONOXIDE-RELEASING MOLECULES, CARBON-MONOXIDE, OXIDATIVE-STRESS, GENE-EXPRESSION, NITRIC-OXIDE, DISEASE, VASOOCCLUSION, INFLAMMATION, MECHANISMS, INDUCTION",

author = "Bains, {Sandip K.} and Roberta Foresti and Jo Howard and Sangeeta Atwal and Green, {Colin J.} and Roberto Motterlini",

year = "2010",

month = feb,

doi = "10.1161/ATVBAHA.109.196360",

language = "English",

volume = "30",

pages = "305--U331",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

TY - JOUR

T1 - Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity

T2 - Effects on Vascular Adhesion and Reactivity

AU - Bains, Sandip K.

AU - Foresti, Roberta

AU - Howard, Jo

AU - Atwal, Sangeeta

AU - Green, Colin J.

AU - Motterlini, Roberto

PY - 2010/2

Y1 - 2010/2

N2 - Objective-Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD.Methods and Results-We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas.Conclusions-Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD. (Arterioscler Thromb Vasc Biol. 2010;30:305-312.)

AB - Objective-Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD.Methods and Results-We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas.Conclusions-Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD. (Arterioscler Thromb Vasc Biol. 2010;30:305-312.)

KW - adhesion

KW - carbon monoxide

KW - endothelium

KW - heme oxygenase

KW - sickle cell disease

KW - MONOXIDE-RELEASING MOLECULES

KW - CARBON-MONOXIDE

KW - OXIDATIVE-STRESS

KW - GENE-EXPRESSION

KW - NITRIC-OXIDE

KW - DISEASE

KW - VASOOCCLUSION

KW - INFLAMMATION

KW - MECHANISMS

KW - INDUCTION

U2 - 10.1161/ATVBAHA.109.196360

DO - 10.1161/ATVBAHA.109.196360

M3 - Article

SN - 1079-5642

VL - 30

SP - 305-U331

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 2

ER -

Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity: Effects on Vascular Adhesion and Reactivity

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this