title: Simvastatin does not diminish the in vivo degeneration of decellularized aortic conduits.
abstract: BACKGROUND
  All present biological cardiovascular prostheses are prone to progressive in vivo degeneration, which can be partially impaired by decellularization. The administration of statins may provide an additional beneficial effect. We provide the first in vivo data on the effect of statins on decellularized cardiovascular implants.
  
  
  METHODS
  Wistar rats with aortic valve insufficiency (day 14) were fed either with a pro-calcific diet (group C; n = 17), or the same diet additionally supplemented with simvastatin (group S; n = 16). Aortic conduits from Sprague-Dawley rats were detergent-decellularized, infrarenally implanted (day 0) in all recipients and explanted at day 28 or day 84.
  
  
  RESULTS
  Sonographic competence of the conduit perfusion was 100%, and overall survival amounted to 97%. Simvastatin decreased the low-density lipoprotein cholesterol serum levels; however, it did not affect the calcification of the implants. Histology revealed alpha-smooth muscle actin-positive intima hyperplasia in both groups. Extensive matrix metalloproteinase activity was observed in calcified areas, especially in group S. Quantitative RNA analysis resulted in no differences with regard to several markers of calcifying degeneration (alkaline phosphatase, osteopontin, osteocalcin, osteoprotegerin, bone morphogenetic protein-2, runt-related transcription factor-2) and inflammation (tumor necrosis factor α, interleukin 1β, receptor for advanced glycation end products, CD39, CD73), but significantly lower levels of interleukin-6 in group S.
  
  
  CONCLUSIONS
  In a standardized small animal model of accelerated cardiovascular calcification, simvastatin failed to diminish the calcification of decellularized aortic conduit implants. This finding confirms the observations of recent clinical trials. However, further experiments are warranted to elucidate the value of partial benefits associated with lower circulating lipid and proinflammatory cytokine levels.
authors.affiliation: *Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany; †Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and ‡Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.forename: Kim
authors.initials: K
authors.lastname: Horstkötter
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiffer
authors.forename: Christofer
authors.initials: C
authors.lastname: Delfs
authors.forename: Kai
authors.initials: K
authors.lastname: Zwirnmann
authors.forename: Mareike
authors.initials: M
authors.lastname: Barth
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001705:Bioprosthesis; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D006349:Heart Valve Diseases / Q000378:metabolism / Q000473:pathology; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D014463:Ultrasonography
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D002118:Calcium