Atherosclerotic plaque morphology and coronary thrombi.
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Body Mass Index↗
Biomedical subjects
Renu Virmani
Publications and source records attributed to Renu Virmani.
A novel rat model of carotid artery stenting for the understanding of restenosis in metabolic diseases.
The effects of risk modifiers such as diabetes, obesity and hypertension on vascular healing after stent deployment are largely unknown, because of a lack of an appropriate animal model to study. Since many inbred strains of rats expressing these phenotypes are available, we validated a carotid artery model of in-stent restenosis in the rat. A detailed histomorphometric analysis was performed on 2-cell Multi-Link(TM) stents (1.5 x 5 mm) deployed in the common carotid artery of male Wistar rats. Early focal thrombus formation around stent struts with adherent leukocytes was evident by day 3. The number of ED-1-positive macrophages was maximal by day 7 and declined markedly thereafter. Neointimal cell proliferation peaked by day 7 (19.3 +/- 6.9) and progressively decreased to <2% by day 60. By day 14, neointimal area was significantly increased (0.39 +/- 0.03 vs. 0.18 +/- 0.05 mm(2) at day 7, p = 0.003) characterized by an enhanced number of alpha-actin-positive smooth muscle cells surrounded by extracellular matrix rich in versican and hyaluronan. At day 28, neointimal area was maximal accompanied by an appreciable decrease in the staining intensity for hyaluronan and versican. By day 60, neointimal area decreased significantly (0.28 +/- 0.04 vs. 0.45 +/- 0.07 mm(2) at day 28, p = 0.04) independent of a change in cell density. This regression phase was accompanied by a marked increase in elastin fibrils and collagen type I. In summary, vascular healing following carotid artery stenting in the rat parallels that of larger animals; however, it is accelerated relative to humans.
Animals↗
In vitro evaluation of vascular endothelial and smooth muscle cell survival and apoptosis in response to hypothermia and freezing.
The success of endovascular techniques such as balloon angioplasty and stenting in the treatment of atherosclerotic vascular disease has been limited by an aggressive proliferative response leading to neointimal hyperplasia and re-stenosis. A new endovascular therapy combining cold treatment with balloon dilation has been proposed to prevent arterial re-stenosis. In order to evaluate the potential of this application, studies were conducted investigating the effects of hypothermia and freezing on human arteries at the cellular level. Cultured arterial endothelial cells and smooth muscle cells were chilled or frozen under controlled thermal conditions. The viability response of the cells was measured with a variety of assays quantifying necrosis, apoptosis, and cell proliferation. These data establish correlations between thermal conditions and the extent and nature of arterial freezing injury. Arterial smooth muscle cells were found to be susceptible to freeze-induced apoptosis in a temperature range of -5 to -15 degrees C. Endovascular cryotherapy designed to induce apoptosis in arterial smooth muscle cells may limit neointimal formation and thereby improve the durability of conventional angioplasty.
Apoptosis↗
First experimental application of bevacizumab-eluting PC coated stent for inhibition of vasa vasorum of atherosclerotic plaque: angiographic results in a rabbit atheromatic model.
INTRODUCTION: Atheromatosis is associated with angiogenesis, through the development of a dense net of vasa vasorum. The role of vascular endothelial growth factor (VEGF) is important in this process. Bevacizumab, an antibody specific for VEGF, has recently been applied in the clinical field. We hypothesized that local delivery of bevacizumab by stent would inhibit the development of vasa vasorum at the stented arterial segment in an atheromatic rabbit model. METHODS: We used 10 New Zealand rabbits under atherogenic diet for 3 weeks. We immersed a BiodivYsio stent into a solution of 4 ml bevacizumab as in previous studies. Both eluting stents and non-eluting BiodivYsio stents were implanted in the middle segment of the 2 iliac arteries of the animals, with the same procedural characteristics. Sacrifice following repeat angiogram was scheduled after 28 days. RESULTS: In all animals the procedure of stent loading with bevacizumab and stent implantation was successful. There was no acute or subacute thrombosis. Iliac artery lumen diameters before and immediately after stent placement were similar in all stent treatment groups. At euthanasia stent lumen diameters were similar in all groups. All stents were angiographically patent at the time of euthanasia without aneurysm formation. Moreover, gross pathologic analysis did not show any evidence of vascular necrosis. CONCLUSIONS: Bevacizumab-eluting stent implantation in atheromatic rabbit iliac arteries is feasible and safe. This new approach for the treatment of stable and vulnerable plaques needs to be further investigated.
Angiogenesis Inhibitors↗