Matrix metalloproteinase inhibition reduces adventitial thickening and collagen accumulation following balloon dilation.
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.
Sierevogel
Marion J
MJ
Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands. m.siervogel@hli.azu.nl
Velema
Evelyn
E
van der Meer
Freek J
FJ
Nijhuis
Manon Oude
MO
Smeets
Mirjam
M
de Kleijn
Dominique P V
DP
Borst
Cornelius
C
Pasterkamp
Gerard
G
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
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen; D003094:Collagen; C100342:marimastat