Myocardial expression analysis of osteopontin and its splice variants in patients affected by end-stage idiopathic or ischemic dilated cardiomyopathy

Abstract

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.

Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation

“…It is also strongly associated with future ischemic stroke in patients with AF during anticoagulant treatment 34 . Recently, it was shown that humans express multiple OPN isoforms that have different functional effects 35 . However, the importance of these isoforms in vascular pathophysiology, CVD, and AF is still elusive.…”

“…34 Recently, it was shown that humans express multiple OPN isoforms that have different functional effects. 35 However, the importance of these isoforms in vascular pathophysiology, CVD, and AF is still elusive.…”

Up-to-date clinical approaches of biomarkers’ use in heart failure

“…There is evidence regarding that the sRANKL/OPG complex may relate to HFrEF development, whereas circulating levels of OPN and OPG corresponded to HFpEF (Berezin and Kremzer, 2014a, c). Moreover, an expression of OPN, OPG and OSN genes in myocardium or vasculature sufficiently distinguished in HFrEF and HFpEF and thereby it has been suggested that BRPs could be markers to suggest the development of different HF phenotypes (Cabiati et al, 2016). Indeed, in the PEACE trial levels of OPN were independently associated with the composite CV outcomes and incident HFpEF hospitalization (Abdalrhim et al, 2016).…”