title: Biomechanics drive histological wall remodeling of neoaortic root: A mathematical model to study the expression levels of ki 67, metalloprotease, and apoptosis transition.
abstract: The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously developed a semiresorbable armored prosthesis able to mechanically sustain the neoaorta preventing dilation and to gradually integrate with the PA wall inducing a progressive arterial-like tissue positive remodeling. We also described the mechanisms of growth, remodeling and stress shielding of the reinforced PA through a mathematical model. We sought to demonstrate the biological counterpart and the potential molecular mechanisms underlying this histological and mechanical remodeling. A specific mathematical model was developed to describe mechanical behavior of the PA. Mallory trichrome red staining and immunohistochemistry for MMP-9 were performed to elucidate extracellular matrix remodeling phenomena. Apoptosis and cell proliferation were determined by TUNEL assay and immunohistochemistry for Ki67, respectively. An histological remodeling phenomenon sustained by increased level of MMP-9, augmented cell proliferation and reduced apoptosis in the reinforced PA was demonstrated. The mathematical model predicted the biomechanical behavior subtended by the histological changes of the PA in these settings. Changes in metalloproteinases (MMP-9), cell proliferation and apoptosis are the main actors in the remodeling process occurring after transposition of the PA into systemic regimens. Use of semiresorbable reinforcements might induce a positive remodeling of the PA in the context of Ross operation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2785-2793, 2016.
authors.affiliation: Department of Cardiac Surgery, Cardiac Surgery Centre, Cardiologique Du Nord De Saint-Denis, Paris, France. francesconappi2@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nappi
authors.affiliation: Department of Structures for Engineering and Architecture and Interdisciplinary Research Center for Biomaterials, University of Napoli Federico II, Napoli, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fraldi
authors.affiliation: Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Clydebank, Glasgow, United Kingdom.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Spadaccio
authors.affiliation: Department of Chemical, Materials and Production Engineering of the University of Naples Federico II, Naples, Italy.
authors.forename: Angelo Rosario
authors.initials: AR
authors.lastname: Carotenuto
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Montagnani
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Castaldo
authors.affiliation: Laboratory of Biosurgical Research, Carpentier Foundation, Pompidou Hospital, University Paris Descartes, Paris, France.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Chachques
authors.affiliation: Department of Cardiovascular Surgery, Hopital De La Salpétriere, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Acar
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000601:surgery; D017209:Apoptosis; D000082882:Bicuspid Aortic Valve Disease; D001696:Biomechanical Phenomena; D001807:Blood Vessel Prosthesis; D003198:Computer Simulation; D006330:Heart Defects, Congenital / Q000601:surgery; D006349:Heart Valve Diseases / Q000601:surgery; D019394:Ki-67 Antigen / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008954:Models, Biological; D011651:Pulmonary Artery / Q000473:pathology* / Q000502:physiology* / Q000601:surgery / Q000648:ultrastructure; D012756:Sheep; D054457:Tissue Scaffolds / Q000737:chemistry; D066253:Vascular Remodeling
chemical_list: D019394:Ki-67 Antigen; D020780:Matrix Metalloproteinase 9
keywords: Ross operation; apoptosis; biomechanical modeling; growth and remodeling; pulmonary artery autograft