Diagnostic Value of Circulating Progranulin and Its Receptor EphA2 in Predicting the Atheroma Burden in Patients with Coronary Artery Disease

Abstract

Background. Progranulin (PGRN) and its potential receptor Eph-receptor tyrosine kinase-type A2 (EphA2) are inflammation-related molecules that present on the atherosclerotic plaques. However, the roles of circulating PGRN and EphA2 in coronary artery disease (CAD) remain unclear. Objective. To study the clinical significance of circulating PGRN and EphA2 levels in Chinese patients undergoing coronary angiography. Methods. Levels of circulating EphA2 fragments and PGRN were examined in 201 consecutive individuals who underwent coronary angiography for suspected CAD in our center from Jan 2020 to Oct 2020. Demographic characteristics, results of biochemical and auxiliary examinations, and other relevant information were collected. The coronary atheroma burden was quantified by the Gensini score and the existence of chronic total occlusion (CTO). Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors for acute coronary syndrome (ACS). In patients with ACS and SAP, a receiver operating characteristic (ROC) curve was generated to detect the accuracy and discriminative ability of levels of EphA2 and PGRN, the Gensini score, and cardiac injury biomarkers as surrogate endpoints for CTO. Results. Circulating EphA2 levels were significantly higher in patients with ACS than in subjects with stable angina pectoris (SAP) or control subjects ( $p<0.001$ ). A positive linear correlation was verified between EphA2 levels and the Gensini score ( $r=0.306$ , $p<0.001$ ), and negative correlation was detected with the left ventricular ejection fraction (LVEF) ( $r=-0.405$ , $p<0.001$ ). Both PGRN and EphA2 were positively associated with cardiac injury biomarkers (i.e., NT-proBNP, cTnT, and hs-CRP) ( $p<0.05$ ). The area under the ROC curve of PGRN and EphA2 was 0.604 and 0.686, respectively ( $p<0.01$ ). Conclusions. Higher circulating EphA2 and PGRN levels were detected in patients with ACS than in patients with SAP. Circulating EphA2 and PGRN levels might be diagnostic factors for predicting the atheroma burden in patients with CAD.