Metalloproteinase inhibition by batimastat does not reduce neointimal thickening in stented atherosclerotic porcine femoral arteries.
BACKGROUND
Vascular injury results in specific temporal patterns of increased matrix metalloproteinase (MMP) activity. MMPs are known to play a role in remodeling and neointimal (NI) thickening. Although in vitro data on the role of metalloproteinases and their inhibitors on smooth muscle cell migration and proliferation are compelling, evidence for inhibition of NI thickening in vivo is inconsistent and is mostly generated in models of balloon angioplasty instead of the more prevalent stent placement. Data from atherosclerotic models are scarce. The objective of the study was to investigate whether the nonspecific MMP inhibitor batimastat, in concentrations known to influence remodeling, could also inhibit NI thickening following stent placement in an atherosclerotic model.


METHODS
Stents were placed in atherosclerotic femoral arteries in Yucatan micropigs on a high cholesterol diet and followed for 6 weeks. Batimastat or vehicle was administered intraperitoneally. NI thickening was assessed by morphometry.


RESULTS
The main finding was that batimastat did not result in a significant decrease in NI thickness. Only following correlation to the amount of preexisting plaque was the difference of 146 microm (19%) statistically significant. Batimastat did not impair wound healing following stenting.


CONCLUSIONS
Batimastat does not significantly influence the degree of NI thickening at 6 weeks following stenting of atherosclerotic porcine femoral arteries, except when correlated to plaque thickness. Batimastat does not affect vascular wound healing.
Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. h.vanbeusekom@erasmusmc.nl
Heleen M M
HM
van Beusekom
Mark J
MJ
Post
Deirdre M
DM
Whelan
Bart J G L
BJ
de Smet
Dirk J
DJ
Duncker
Wim J
WJ
van der Giessen
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000628:therapy; D005263:Femoral Artery / Q000187:drug effects* / Q000473:pathology; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D061965:Matrix Metalloproteinase Inhibitors; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D013556:Swine, Miniature; D013876:Thiophenes / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat