Metalloproteinase inhibition by batimastat does not reduce neointimal thickening in stented atherosclerotic porcine femoral arteries
Cardiovascular Radiation Medicine , Volume 4 - Issue 4 p. 186- 191
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 μm (19%) statistically significant. Batimastat did not impair wound healing following stenting. Conclusion 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.
|Atherosclerosis, Metalloproteinases, NI thickening, Stents, Swine model|
|Cardiovascular Radiation Medicine|
|Organisation||Department of Cardiology|
van Beusekom, H.M.M, Post, M.J, Whelan, D.M, de Smet, B.J.G.L, Duncker, D.J.G.M, & van der Giessen, W.J. (2003). Metalloproteinase inhibition by batimastat does not reduce neointimal thickening in stented atherosclerotic porcine femoral arteries. Cardiovascular Radiation Medicine, 4(4), 186–191. doi:10.1016/j.carrad.2004.02.004