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

Michel T. Corban, Abhiram Prasad, Lisa Nesbitt, Darrell Loeffler, Joerg Herrmann, Lilach O Lerman, Amir Lerman

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3 Citations (Scopus)

Abstract

Background-Soluble urokinase plasminogen activator receptor (suPAR) 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 suPAR 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 suPAR and PAI-1 levels were measured in each patient before acetylcholine administration, and cross-coronary suPAR 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 suPAR production versus suPAR 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-suPAR 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.

Original languageEnglish (US)
Article numbere009881
JournalJournal of the American Heart Association
Volume7
Issue number15
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

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Urokinase Plasminogen Activator Receptors
Coronary Circulation
Plasminogen Activator Inhibitor 1
Acetylcholine
Hemodynamics
Coronary Sinus
Fibrinolysis
Fibrin
Coronary Artery Disease
Atherosclerosis
Coronary Vessels
Thrombosis
Biomarkers

Keywords

  • Coronary circulation
  • Endothelial dysfunction
  • Epicardial
  • Microvascular dysfunction
  • Plasminogen activator
  • Soluble urokinase plasminogen activator receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{7025924d1670452e8ed26f6af356543f,
title = "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 (suPAR) 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 suPAR 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 suPAR and PAI-1 levels were measured in each patient before acetylcholine administration, and cross-coronary suPAR 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 suPAR production versus suPAR 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-suPAR 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.",
keywords = "Coronary circulation, Endothelial dysfunction, Epicardial, Microvascular dysfunction, Plasminogen activator, Soluble urokinase plasminogen activator receptor",
author = "Corban, {Michel T.} and Abhiram Prasad and Lisa Nesbitt and Darrell Loeffler and Joerg Herrmann and Lerman, {Lilach O} and Amir Lerman",
year = "2018",
month = "8",
day = "1",
doi = "10.1161/JAHA.118.009881",
language = "English (US)",
volume = "7",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "15",

}

TY - JOUR

T1 - 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

AU - Corban, Michel T.

AU - Prasad, Abhiram

AU - Nesbitt, Lisa

AU - Loeffler, Darrell

AU - Herrmann, Joerg

AU - Lerman, Lilach O

AU - Lerman, Amir

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Background-Soluble urokinase plasminogen activator receptor (suPAR) 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 suPAR 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 suPAR and PAI-1 levels were measured in each patient before acetylcholine administration, and cross-coronary suPAR 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 suPAR production versus suPAR 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-suPAR 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.

AB - Background-Soluble urokinase plasminogen activator receptor (suPAR) 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 suPAR 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 suPAR and PAI-1 levels were measured in each patient before acetylcholine administration, and cross-coronary suPAR 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 suPAR production versus suPAR 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-suPAR 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.

KW - Coronary circulation

KW - Endothelial dysfunction

KW - Epicardial

KW - Microvascular dysfunction

KW - Plasminogen activator

KW - Soluble urokinase plasminogen activator receptor

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U2 - 10.1161/JAHA.118.009881

DO - 10.1161/JAHA.118.009881

M3 - Article

C2 - 30371230

AN - SCOPUS:85051441770

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 15

M1 - e009881

ER -