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

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.