title: Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis.
abstract: OBJECTIVE
  To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury.
  
  
  BACKGROUND
  VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms.
  
  
  METHODS
  Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed.
  
  
  RESULTS
  Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls.
  
  
  CONCLUSIONS
  VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.
authors.affiliation: CNRS UMR 7054, Centre de Recherches Chirurgicales, Université Paris XII, UFR de médecine, Hôpital H. Mondor, AP-HP Créteil, France. allaire@club-ineternet.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Allaire
authors.forename: Béatrice
authors.initials: B
authors.lastname: Muscatelli-Groux
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Guinault
authors.forename: Carine
authors.initials: C
authors.lastname: Pages
authors.forename: Audrey
authors.initials: A
authors.lastname: Goussard
authors.forename: Chantal
authors.initials: C
authors.lastname: Mandet
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Didier
authors.initials: D
authors.lastname: Méllière
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Becquemin
mesh_terms: D000818:Animals; D001014:Aortic Aneurysm / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D002404:Catheterization; D017690:Cell Transplantation; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D007249:Inflammation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D011506:Proteins