P6450Plasminogen activator inhibitor type-1 (PAI-1) expression relates to the presence of myocardial inflammation in patients with nonischemic cardiomyopathy

Abstract

Abstract Background Plasminogen activator inhibitor type-1 (PAI-1) is an important inhibitor of the fibrinolytic pathway and an acute phase reactant in response to inflammatory cytokines, resulting in thrombosis, arteriosclerosis, and tissue fibrosis. It has been identified as a potential biomarker for coronary artery disease and metabolic syndrom. However, so far, nothing is known about its importance in nonischemic cardiomyopathy. Aims To analyzed PAI-1 expression in patients with different forms of cardiomyopathies and evaluate possible influence of PAI-1-dependent pathomechanisms in patients with intramyocardial inflammation. Methods and results In this study, endomyocardial biopsies (EMBs) from 309 patients (mean age 48.0±13.9 years) with different forms of cardiomyopathies were enrolled, including 123 patients with dilated cardiomyopathy (DCM) (mean LVEF 28.01±9.06%) and 186 patients with EMB-proven virus-negative inflammatory cardiomyopathy (DCMi) (mean LVEF 31.76±14.14%). 10 patients (mean LVEF 60.50±4.76%) without viral or inflammation in EMB served as controls. Hemodynamic parameters were measured by catheterization and echocardiography. EMBs were performed at first admission after exclusion of ischemic of valvular heart disease. In EMBs PAI-1 was assessed by immunohistology including digital imaging analysis. PAI-1 expression was significantly higher in patients with DCMi in contrast to DCM patients and controls (0.517±2.20 vs. 0.187±0.598 vs. 0.023±0.032% Area Fraction; p=0.0002). PAI-expression correlates significantly with lymphocytic infiltrates (for CD3 r=0.56, p<0.0001, and LFA-1 r=0.59, p<0.0001). This was found to be independent of hemodynamic parameters, and age. Conclusion Myocardial inflammation is associated with a significant increase in PAI-1 expression in DCMi independently of the hemodynamic conditions. This new pathophysiological axis could be a potiential therapeutic target in future treatment stategies in DCMi.