Elevated plasma t-PA (tissue plasminogen activator) and serum CRP (C-reactive protein) concentrations are associated with an adverse cardiovascular risk. In the present study, we investigated whether acute local inflammation causes vascular dysfunction and influences t-PA release in patients with stable coronary heart disease. Serum CRP, plasma t-PA and PAI-1 (plasminogen activator inhibitor type 1) concentrations were determined in 95 patients with stable coronary heart disease. A representative subpopulation of 12 male patients received an intra-brachial infusion of TNF-α (tumour necrosis factor-α) and saline placebo using a randomized double-blind cross-over study design. Forearm blood flow and plasma fibrinolytic and inflammatory variables were measured. Serum CRP concentrations correlated with plasma t-PA concentrations (r=0.37, P<0.001) and t-PA/PAI-1 ratio (r=−0.21, P<0.05). Intra-arterial TNF-α caused a rise in t-PA concentrations (P<0.001) without affecting blood flow or PAI-1 concentrations. TNF-α pretreatment impaired acetylcholine- and sodium nitroprusside-induced vasodilatation (P<0.001 for both) whilst doubling bradykinin-induced t-PA release (P=0.006). In patients with stable coronary heart disease, plasma fibrinolytic factors correlate with a systemic inflammatory marker and local vascular inflammation directly impairs vasomotor function whilst enhancing endothelial t-PA release. We suggest that the adverse prognosis associated with elevated plasma t-PA concentrations relates to the underlying causative association with vascular inflammation and injury.
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March 2006
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Research Article|
February 10 2006
Vascular and fibrinolytic effects of intra-arterial tumour necrosis factor-α in patients with coronary heart disease
Simon D. Robinson;
*Centre for Cardiovascular Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, U.K.
Correspondence: Dr Simon D. Robinson (email [email protected]).
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Pamela Dawson;
Pamela Dawson
†Department of Haematology, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, U.K.
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Christopher A. Ludlam;
Christopher A. Ludlam
†Department of Haematology, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, U.K.
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Nicholas A. Boon;
Nicholas A. Boon
‡Department of Cardiology, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, U.K.
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David E. Newby
David E. Newby
*Centre for Cardiovascular Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, U.K.
‡Department of Cardiology, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, U.K.
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Publisher: Portland Press Ltd
Received:
August 24 2005
Revision Received:
November 03 2005
Accepted:
November 25 2005
Accepted Manuscript online:
November 25 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2006
Clin Sci (Lond) (2006) 110 (3): 353–360.
Article history
Received:
August 24 2005
Revision Received:
November 03 2005
Accepted:
November 25 2005
Accepted Manuscript online:
November 25 2005
Connected Content
This is a commentary on:
Local inflammation, endothelial dysfunction and fibrinolysis in coronary heart disease
Citation
Simon D. Robinson, Pamela Dawson, Christopher A. Ludlam, Nicholas A. Boon, David E. Newby; Vascular and fibrinolytic effects of intra-arterial tumour necrosis factor-α in patients with coronary heart disease. Clin Sci (Lond) 1 March 2006; 110 (3): 353–360. doi: https://doi.org/10.1042/CS20050268
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