Angiogenesis: initiation and maintenance.
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Biomedical subjects
Mark J Post
Publications and source records attributed to Mark J Post.
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. 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.
Angioplasty, Balloon↗
Evaluation of the porcine ameroid constrictor model of myocardial ischemia for therapeutic angiogenesis studies.
The porcine ameroid model of chronic myocardial ischemia has been widely used for the evaluation of coronary collateralization development. The impact of target vessel occlusion on the presence of myocardial ischemia, and the relationship between morphological, functional, and hemodynamic measurements in the context of therapeutic angiogenesis studies, however, has not been studied thus far. The authors therefore performed a systematic analysis of 94 animals undergoing ameroid constrictor placement around the left circumflex coronary artery (LCX) and, furthermore, a comprehensive evaluation including echocardiography and coronary angiography 26 +/- 1 (mean +/- SEM) days after ameroid placement. Complete LCX occlusion was observed in 34/94 animals (36%) and identified those with myocardial ischemia of the lateral wall, both at rest and under pharmacological stress. By applying a set of angiographic criteria (TIMI or= 1), another 27/94 animals with myocardial ischemia under conditions of pharmacological stress conditions could be identified. Interestingly, echocardiographic parameters of regional and global myocardial function were not correlated with myocardial blood flow or the degree of ischemia. There was no relationship between the extent of coronary collateralization, as assessed by angiography, echocardiographic parameters, or myocardial blood flow. The authors therefore conclude that complete occlusion of the ameroid instrumented coronary artery is not a prerequisite for successfully establishing the pathophysiology of myocardial ischemia. Defined angiographic criteria are important in identifying ischemic animals, thus reducing total animal numbers. Angiographic assessment of the degree of coronary collateralization, however, is not associated with myocardial blood flow or function and should not be used as a primary outcome measure of therapeutic angiogenesis studies in this model.
Animals↗