title: 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 full-length 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.
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cabiati
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.|Laboratory of Translational Critical Care Medicine, Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Svezia
authors.affiliation: Laboratory of Translational Critical Care Medicine, Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Matteucci
authors.affiliation: Department of cardiac Surgery, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Botta
authors.affiliation: Department of Pathology, University Hospital Pisa, Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Pucci
authors.affiliation: Cardiac Surgery Department, Cardiothoracic Department, A.O.U. Città della Salute e della Scienza di Torino, Presidio Molinette, and University of Torino, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Rinaldi
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Caselli
authors.affiliation: Laboratory of Translational Critical Care Medicine, Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Ry
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013917:Thrombin / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D053495:Osteopontin; D013917:Thrombin