Myocardial Expression Analysis of Osteopontin and Its Splice Variants in Patients Affected by End-Stage Idiopathic or Ischemic Dilated Cardiomyopathy

Osteopontin (OPN) is a phosphoglycoprotein of cardiac extracellular matrix and it is still poorly defined whether its expression changes in failing heart of different origin. The fulllength OPN-a and its isoforms (OPN-b, OPN-c) transcriptomic profile were evaluated in myocardium of patients with dilated or ischemic cardiomyopathy (DCM n = 8; LVEF% = 17.5 +/- 3; ICM n = 8; LVEF% = 19.5 +/- 5.2) and in auricle of valvular patients (VLP n = 5; LVEF % +/- 50), by Real-time PCR analysis. OPN-a and thrombin mRNA levels resulted significantly higher in DCM compared to ICM patients (DCM: 31.3 +/- 7.4, ICM: 2.7 +/- 1.1, p = 0.0002; DCM: 19.1 +/- 4.9, ICM: 5.4 +/- 2.2, p = 0.007, respectively). Although both genes' mRNA levels increased in patients with LVEF< 50% (DCM+ ICM) with respect to VLP with LVEF> 50%, a significant increase in OPN (p = 0.0004) and thrombin (p = 0.001) expression was observed only in DCM. In addition, a correlation between OPN-a and thrombin was found in patients with LVEF< 50% (r = 0.6; p = 0.003). The mRNA pattern was confirmed by OPN-a cardiac protein concentration (VLP: 1.127 +/- 0.26; DCM: 1.29 +/- 0.22; ICM: 1.00 +/- 0.077 ng/ml). The OPN splice variants expression were detectable only in ICM (OPN-b: 0.357 +/- 0.273; OPN-c: 0.091 +/- 0.033) and not in DCM patients. A significant correlation was observed between collagen type I, evaluated by immunohistochemistry analysis, and both OPN-a mRNA expression (r = 0.87, p = 0.002) and OPN protein concentrations (r = 0.77, p = 0.016). Concluding, OPN-a and thrombin mRNA resulted dependent on the origin of heart failure while OPN-b and OPN-c highlighted a different expression for DCM and ICM patients, suggesting their correlation with different clinical-pathophysiological setting.