Myocardial gene expression of osteopontin is higher in idiopathic than ischemic end-stage dilated cardiomyopathy

Purpose: The morphological and molecular features of cardiac remodelling are similar in idiopathic (DCM) as well as ischemic (ICM) human end-stage cardiomyopathy. However, the hallmarks of cardiac remodelling typical of DCM may be helpful to identify new treatment targets. Osteopontin (OPN), a phosphoglycoprotein of cardiac extracellular matrix, is an emerging mediator of cardiac inflammation and fibrosis in failing hearts. We have investigated whether the myocardial levels of OPN were affected by etiology of heart failure in the presence of similar left ventricular ejection fraction (LVEF). Methods: mRNA and protein levels of OPN were measured in LV samples from failing DCM (n=8; age: <50yrs; LVEF%=17.5±3; LVEDV=305.5±110ml) and ICM patients (n=8; age: <50yrs; LVEF%=19.5±5.2; LVEDV=270±97 ml) undergoing cardiac transplantation. All patients received conventional therapy for HF and underwent to cardiac function evaluation. As control (C), atrial samples of age and sex matched normal subjects (LVEF% ≥50) were analyzed. Real-time PCR analysis was carried out to measure OPN gene expression and data were normalized to three genes (RPS4X, eEF1a, RPL13a). The protein levels of OPN were assessed by enzyme immunometric assay. Results: Even though the extent of interstitial fibrosis in ICM was higher than DCM, OPN mRNA was significantly increased in DCM compared to C and ICM patients (C: 2.2±0.3; DCM: 31.3±7.4; ICM: 2.7±1.1, p=0.0004 C vs DCM and p=0.0002 DCM vs ICM). A similarly trend was observed for OPN cardiac protein concentration (C: 1.127±0.26; DCM: 1.29±0.22; ICM: 1.00±0.077 ng/ml). Conclusion: We have detected higher levels of OPN gene expression in LV samples of DCM rather than ICM failing hearts in the presence of similar LVEF. Our data suggest the new role of OPN as biomarker of myocardial remodelling typical of DCM independently of the fibrosis degree.