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

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Amir Lerman¹  Michel T. Corban¹  Lisa Nesbitt¹  Darrell Loeffler¹  Lilach O. Lerman¹  Abhiram Prasad¹  Joerg Herrmann¹ 

[1] Department of Cardiovascular Diseases Mayo Clinic College of Medicine and Science Rochester MN;

关键词: coronary circulation;    endothelial dysfunction;    epicardial;    microvascular dysfunction;    plasminogen activator;    soluble urokinase plasminogen activator receptor;   

DOI  :  10.1161/JAHA.118.009881

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown