title: Complete loss of functional smooth muscle cells precedes vascular remodeling in rat aorta allografts.
abstract: BACKGROUND
  The functional consequences of vascular remodeling in rat aorta allografts were studied at different times after transplantation (Tx).
  
  
  METHODS
  At days 1, 3, 7, 14, 28, and 56 after Tx, rat aorta allografts (Dark Agouti [DA]-to-Lewis) were mounted as isolated organs, and their contractile properties tested with phenylephrine, KCl, or endothelin-1. Controls were native DA-aortae and DA-syngeneic grafts. Changes in alpha smooth muscle actin and morphology were assessed by immunoblotting and histology.
  
  
  RESULTS
  PostTx syngeneic grafts presented similar functional and morphological properties to native aortae. In allografts, no morphological changes was detected at day 7 after Tx, but phenylephrine-induced vasoconstriction was reduced by 60%. Signs of medial smooth muscle cell (SMC) loss and adventitial inflammation were observed at day 14 after Tx, without neointima formation. A complete loss of contractile property was observed at day 28 after Tx in association with a 75% decrease in alpha-SMC actin, severe adventitial inflammation, and reduced medial cellularity. At this time, neointima was restricted to both edges of allografts. At day 56 after Tx, allografts were also not functional and exhibited neointima on their entire length. All these changes were prevented by treating recipients with cyclosporine (7.5 mg/kg/day).
  
  
  CONCLUSIONS
  These results indicate that, after Tx, the contractile property of rat aorta allografts is altered before manifest vascular remodeling. Because this can be prevented by cyclosporine, it most likely reflects an acute rejection of SMC. These results also show that vascular graft dysfunction can be used to monitor the development of rejection in the rat aorta allograft model.
authors.affiliation: Novartis Pharma AG, Transplantation Research, Basel, Switzerland. Marc.Bigaud@Pharma.Novartis.com
authors.forename: M
authors.initials: M
authors.lastname: Bigaud
authors.forename: E O
authors.initials: EO
authors.lastname: Schraa
authors.forename: E
authors.initials: E
authors.lastname: Andriambeloson
authors.forename: V
authors.initials: V
authors.lastname: Lobstein
authors.forename: C
authors.initials: C
authors.lastname: Pally
authors.forename: T
authors.initials: T
authors.lastname: Kobel
authors.forename: C
authors.initials: C
authors.lastname: Bruns
authors.forename: H G
authors.initials: HG
authors.lastname: Zerwes
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology* / Q000637:transplantation*; D019332:Endothelin-1 / Q000494:pharmacology; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011184:Postoperative Period; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014185:Transplantation, Isogeneic; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000199:Actins; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011188:Potassium