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Local Production of Soluble Urokinase Plasminogen Activator Receptor and Plasminogen Activator Inhibitor-1 in the Coronary Circulation Is Associated With Coronary Endothelial Dysfunction in Humans.

Abstract：

:Background Soluble urokinase plasminogen activator receptor (su PAR ) is a proinflammatory biomarker associated with immune activation and fibrinolysis inhibition. Plasminogen activator inhibitor ( PAI -1) is associated with excessive fibrin accumulation, thrombus formation, and atherosclerosis. The relationship between cross-coronary su PAR and PAI -1 production and endothelial dysfunction remains unknown. Methods and Results Seventy-nine patients (age 53±10 years, 75% women) with angina and normal coronary arteries or mild coronary artery disease (<40% stenosis) on angiogram underwent acetylcholine assessment of epicardial endothelial dysfunction (mid-left anterior descending coronary artery diameter decrease >20% after acetylcholine) and mircovascular endothelial dysfunction (coronary blood flow change <50% after acetylcholine). Simultaneous left main and coronary sinus su PAR and PAI -1 levels were measured in each patient before acetylcholine administration, and cross-coronary su PAR and PAI -1 production rates were calculated. Patients' characteristics, except for age (51±10 versus 57±9, P=0.02), and resting coronary hemodynamics were not significantly different between patients with (26%) versus without (74%) epicardial endothelial dysfunction. Patients' characteristics and resting coronary hemodynamics were not significantly different between those with (62%) and those without (38%) mircovascular endothelial dysfunction. Patients with mircovascular endothelial dysfunction demonstrated local coronary su PAR production versus su PAR extraction in patients with normal microvascular function (median 25.8 [interquartile range 121.6, -23.7] versus -12.7 [52.0, -74.8] ng/min, P=0.03). Patients with epicardial endothelial dysfunction had higher median coronary PAI -1 production rates compared with those with normal epicardial endothelial function (1224.7 [12 940.7, -1915.4] versus -187.4 [4444.7, -4535.8] ng/min, P=0.03). Conclusions su PAR is released in coronary circulation of patients with mircovascular endothelial dysfunction and extracted in those with normal microvascular function. Cross-coronary PAI -1 release is higher in humans with epicardial endothelial dysfunction.

journal_name

J Am Heart Assoc

journal_title

Journal of the American Heart Association

authors

Corban MT,Prasad A,Nesbitt L,Loeffler D,Herrmann J,Lerman LO,Lerman A

doi

10.1161/JAHA.118.009881

subject

Has Abstract

pub_date

2018-08-07 00:00:00

pages

e009881

issue

issn

2047-9980

journal_volume

pub_type

杂志文章

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Local Production of Soluble Urokinase Plasminogen Activator Receptor and Plasminogen Activator Inhibitor-1 in the Coronary Circulation Is Associated With Coronary Endothelial Dysfunction in Humans.