Heightened systemic oxidative stress is increasingly recognized as a feature of cystic fibrosis (CF). The consequences of long-term exposure to free radical attack include a predisposition to diseases such as cancer and atherosclerosis. An increased incidence of malignancy among adult patients with CF has been reported, but the absence of atherosclerotic disease is well described. The aim of the present study was to assess endothelial function in vivo and relate this to the potential of serum from patients with CF to induce oxidative-mediated damage in cultured human endothelial cells. A group of 11 CF patients was matched with a group of healthy volunteers with regard to age and sex. Endothelial function was assessed as endothelium-dependent and -independent vasodilation by measuring forearm blood flow in response to infused acetylcholine and sodium nitroprusside respectively. Confluent monolayers of cultured human endothelial cells were exposed to serum from CF patients and control subjects. Following exposure, cell death was assessed by lactate dehydrogenase release, and the degree of lipid peroxidation in the membrane was assessed by measuring the content of lipid hydroperoxides, malondialdehyde and 4-hydroxynonenal. Endothelial monolayers exposed to serum from CF patients released significantly less lactate dehydrogenase following exposure than those exposed to serum from healthy controls (1.8% and 3.0% respectively; mean difference -1.2%; 95% confidence intervals -1.9% to -0.1%; P < 0.05) and contained significantly less 4-hydroxynonenal (0.75 and 3.41μmol/g of protein respectively; mean difference -2.66μmol/g; 95% confidence intervals -5.10 to -0.22μmol/g; P < 0.05). There was no significant difference between patients and controls in the extent of serum-induced membrane peroxidation, as assessed by malondialdehyde or lipid hydroperoxides, or in endothelial function, as assessed by forearm blood flow. In conclusion, despite evidence for heightened systemic oxidative stress in CF, patients displayed no impairment of endothelial function, and their serum caused significantly less damage to human endothelial cells than that from matched controls.
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Research Article|
September 27 2001
Individuals with cystic fibrosis do not display impaired endothelial function or evidence of oxidative damage in endothelial cells exposed to serum
Lawrence T. McGRATH;
*Department of Therapeutics and Pharmacology, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
Correspondence: Dr L. T. McGrath (e-mail [email protected]).
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Damien McCALL;
Damien McCALL
*Department of Therapeutics and Pharmacology, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
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Colm G. HANRATTY;
Colm G. HANRATTY
*Department of Therapeutics and Pharmacology, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
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Siobhan BRENNAN;
Siobhan BRENNAN
†Department of Geriatric Medicine, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
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Adrian DEVINE;
Adrian DEVINE
*Department of Therapeutics and Pharmacology, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
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Daniel F. McCAULEY;
Daniel F. McCAULEY
*Department of Therapeutics and Pharmacology, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
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Bernard SILKE;
Bernard SILKE
*Department of Therapeutics and Pharmacology, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
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Stuart ELBORN
Stuart ELBORN
‡Adult Cystic Fibrosis Unit, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, U.K.
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Publisher: Portland Press Ltd
Received:
April 03 2001
Revision Received:
May 29 2001
Accepted:
July 09 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 101 (5): 507–513.
Article history
Received:
April 03 2001
Revision Received:
May 29 2001
Accepted:
July 09 2001
Citation
Lawrence T. McGRATH, Damien McCALL, Colm G. HANRATTY, Siobhan BRENNAN, Adrian DEVINE, Daniel F. McCAULEY, Bernard SILKE, Stuart ELBORN; Individuals with cystic fibrosis do not display impaired endothelial function or evidence of oxidative damage in endothelial cells exposed to serum. Clin Sci (Lond) 1 November 2001; 101 (5): 507–513. doi: https://doi.org/10.1042/cs1010507
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