title: Mitral valve endothelial cells secrete osteoprotegerin during endothelial mesenchymal transition.
abstract: Mitral valve prolapse (MVP) has a prevalence of 3% in the general population, affecting >176 million people worldwide. Despite this, little is known about the molecular and cellular mechanisms involved in the progression of MVP and surgical intervention is the only available option. In this study we investigated the role of osteoprotegerin (OPG) during endothelial to mesenchymal transition (EndMT) in MVP.
  
  
  
  VECs and VICs were isolated from posterior mitral valve leaflets of patients undergoing mitral valve repair (n=25). Plasma was collected from 57 subjects (29 controls and 28 MVP patients). Overexpression of OPG during EndMT followed by autocrine effects characterised by reactive oxygen species increment and accelerated migration was documented. In addition, OPG increased VIC proliferation. Finally, OPG plasma levels were significantly higher in MVP patients compared to control subjects and the area under the ROC curve was 0.92.
  
  
  
  EndMT has been recognised as a possible pathological mechanism for MVP. For the first time, we report the involvement of OPG in cellular and molecular changes in MVP isolated cells. In addition, we detected elevated circulating OPG levels in MVP patients when compared to controls, which supports the hypothesis that OPG is involved in MVP development and progression.
authors.affiliation: Centro Cardiologico Monzino IRCCS, Milan, Italy; Università degli Studi di Milano, Dipartimento di Scienze Farmacologiche e Biomolecolari, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Songia
authors.affiliation: University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Branchetti
authors.affiliation: Policlinico San Donato IRCCS, U.O. Cardiochirurgia e Ricerca traslazionale, San Donato Milanese, Italy; Università degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Parolari
authors.affiliation: Centro Cardiologico Monzino IRCCS, Milan, Italy.
authors.forename: Veronika
authors.initials: V
authors.lastname: Myasoedova
authors.affiliation: University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Centro Cardiologico Monzino IRCCS, Milan, Italy; Università degli Studi di Milano, Dipartimento di Scienze Cliniche e di Comunità, Sezione Cardiovascolare, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Alamanni
authors.affiliation: Centro Cardiologico Monzino IRCCS, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Centro Cardiologico Monzino IRCCS, Milan, Italy. Electronic address: Paolo.Poggio@ccfm.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Poggio
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003239:Connective Tissue Cells / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008943:Mitral Valve / Q000378:metabolism* / Q000473:pathology*; D008945:Mitral Valve Prolapse / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053244:Osteoprotegerin; D017382:Reactive Oxygen Species; D003094:Collagen; D020782:Matrix Metalloproteinases
keywords: Circulating marker; Endothelial to mesenchymal transition; Mitral valve prolapse; Valve endothelial cells; Valve interstitial cells