Balloon angioplasty has become a popular technique for the treatment of atherosclerotic lesions. However, angioplasty has one very significant problem - in up to half of the successfully treated clinical cases, the lesions reappears, usually within 6 to 12 months. This recurrence or restenosis is the result of intimal thickening, secondary to cell proliferation and extracellular matrix deposition, and a failure of the artery to remodel. The overall objective of the proposed research is to determine if restenosis after balloon angioplasty of the rabbit iliac arteries can be prevented by coating the luminal surface of the dilated artery with endothelial cells previously obtained from the rabbit's adipose tissue.
The first aim of this study is to determine the method which provides maximal endothelial cell retention on the luminal surface of the balloon dilated artery. In vitro experiments will be performed to determine if the adhesion of the endothelial cells to matrix can be augmented by stimulating integrin and/or non-integrin mediated adhesion. Endothelial cell adhesion will be measured under static conditions (retention on matrix-coated culture cells) and dynamic conditions (retention on matrix-coated microscope slides placed in a parallel plate flow apparatus and exposed to shear). Integrin-mediated adhesion will be augmented by treating the endothelial cells with protein kinase C activators, growth factors, or protein kinase A inhibitors. Non-integrin mediated adhesion will be promoted by simulating transglutaminase activity. Additional short term in vivo experiments, which measure the adhesion and retention of fluorescently-labeled endothelial cells to balloon dilated rabbit external iliac arteries using epifluorescence microscopy, will be performed to determine if simulation of integrin or non-integrin mediated endothelial cell adhesion improves endothelial cell retention, and if modifications to the cell delivery technique can improve cell retention. Modifications that will be tested include rotation of the rabbit during endothelial cell placement.
The second aim of this study is to determine if the placement of endothelial cells on the luminal surface of balloon dilated arteries, using the method which provides maximal endothelial cell coverage, will reduce intimal thickening and promote arterial enlargement. Long-term in vivo experiments will be performed in which the method that provides the best endothelial cell retention will be used to place endothelial cells on one balloon dilated rabbit iliac artery; the contralateral balloon-dilated iliac artery will serve as a control. Four weeks thereafter, the effectiveness of the re-endothelialization procedure will be determined by comparing arteriographic diameters, intimal areas, and circumferences of internal and elastic laminae for the treatment of control arteries.
| Wu, Xiaodong; Luke, Amy; Cooper, Richard S et al. (2004) A genome scan among Nigerians linking resting energy expenditure to chromosome 16. Obes Res 12:577-81 |
| Dillavou, E; Cupp, P; Consigny, P M (2001) Delivery of endothelial cells to balloon-dilated rabbit arteries with use of a local delivery catheter. J Vasc Interv Radiol 12:601-5 |
| Consigny, P M (2000) Endothelial cell seeding on prosthetic surfaces. J Long Term Eff Med Implants 10:79-95 |
| Consigny, P M; Silverberg, D A; Vitali, N J (1999) Use of endothelial cells containing superparamagnetic microspheres to improve endothelial cell delivery to arterial surfaces after angioplasty. J Vasc Interv Radiol 10:155-63 |
| Consigny, P M; Vitali, N J (1998) Resistance of freshly adherent endothelial cells to detachment by shear stress is matrix and time dependent. J Vasc Interv Radiol 9:479-85 |
| Consigny, P M (1997) Placement of endothelial cells on the luminal surface of denuded arteries in vitro and in vivo. J Vasc Interv Radiol 8:595-604 |
