title: Matrix metalloproteinase inhibition reduces adventitial thickening and collagen accumulation following balloon dilation.
abstract: OBJECTIVE
  Constrictive arterial remodeling following balloon angioplasty has been related to adventitial collagen accumulation and subsequent thickening and can be prevented by matrix metalloproteinase (MMP) inhibition. Following balloon dilation, we examined the effect of MMP inhibition on collagen turnover and the relationship between adventitial area and degree of constrictive remodeling.
  
  
  METHODS
  In 12 non-atherosclerotic landrace pigs, balloon dilation was performed in 39 peripheral arteries with and without MMP inhibition. Follow up with intravascular ultrasound was performed at 42 days. Collagen content was quantified using polarized light and digital image microscopy. Procollagen expression was determined using immunochemistry and Western blotting.
  
  
  RESULTS
  In the MMP inhibitor group, constrictive remodeling was inhibited at 42 days follow up. In control and MMP inhibitor groups, a positive relation was observed between adventitial thickness and degree of constrictive remodeling (P<0.001). Adventitial thickening and adventitial collagen content were reduced in the MMP inhibitor group (P=0.002 and P=0.001, respectively). Procollagen immunostaining, but not protein analysis on Western blotting, was decreased in the MMP inhibitor group.
  
  
  CONCLUSIONS
  MMP inhibition impaired adventitial thickening by reduction of collagen content 42 days after balloon dilation. This might explain its inhibitory effect on constrictive remodeling.
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands. m.siervogel@hli.azu.nl
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Sierevogel
authors.forename: Evelyn
authors.initials: E
authors.lastname: Velema
authors.forename: Freek J
authors.initials: FJ
authors.lastname: van der Meer
authors.forename: Manon Oude
authors.initials: MO
authors.lastname: Nijhuis
authors.forename: Mirjam
authors.initials: M
authors.lastname: Smeets
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Cornelius
authors.initials: C
authors.lastname: Borst
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000818:Animals; D001158:Arteries; D015153:Blotting, Western / Q000379:methods; D002404:Catheterization / Q000009:adverse effects*; D003094:Collagen / Q000032:analysis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen / Q000032:analysis; D013552:Swine; D017539:Tunica Intima / Q000000981:diagnostic imaging* / Q000378:metabolism; D018084:Ultrasonography, Interventional
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen; D003094:Collagen; C100342:marimastat