Restenosis cell migration

The calcification of atherosclerotic plaques may be induced by osteopontin expression, since osteopontin is a protein with a well-characterized role in bone formation and calcification. Vascular smooth muscle cell migration on osteopontin is dq endent on the integrin av 33 and antagonists of av 33 prevent both smooth muscle cell migration and restenosis in some animal model [8]. 

The unique mechanism of action of Taxol and its ability to act synergistically with other chemotherapeutic agents have resulted in the establishment of Taxol as a useful chemotherapeutic agent for selected cancers. Furthermore, the ability of Taxol to suppress cell migration and proliferation hold much promise for the use of Taxol for the prevention of restenosis as well as other conditions involving the inhibition of cell migration. 

Pemirolast Inhibition of smooth muscle cell proliferation and migration Ohsawa (55) Low restenosis and neointimal hyperplasia... 

As previously mentioned, for SMC proliferation after coronary angioplasty, cell activation and cell-to-cell interaction of platelets and leukocytes mediated by adhesion molecules are considered to be important. Coronary stenting produces the release of an adhesion molecule, P-selectin, from d-granule of activated platelets. P-selectin-mediated platelet-leukocyte interaction has a crucial role in the development of stent restenosis. Cilostazol is an antiplatelet, antithrombotic, phosphodiesterase III inhibitor that by inhibiting P-selectin release has inhibitory effects on SMC migration. In addition, cilostazol may directly act to inhibit intimal hyperplasia. 

WiskirchenJ, Schober W, Schart N, et al. The effects of pacli-taxel on the three phases of restenosis smooth muscle cell proliferation, migration, and matrix formation an in vitro study. Invest Radiol 2004 39(9) 565-57l. 

Initial attempts at treating or preventing restenosis focused primarily on inhibition of the proliferation of vascular SMCs (VSMCs). A series of agents successful at inhibition of SMC proliferation in vitro as well as in vivo in animal models such as carotid injury models in the rat failed to demonstrate benefit in the clinic. More recently, it has been shown in addition to effects on SMCs, that mechanical intervention also activates the recruitment and activation of immune cells. Cell signaling through cytokines, chemokines, and adhesion molecule expression results in the recruitment to the vascular wall of cells of many types, as well as their proliferation, migration, and/or maturation. 

The narrowing of the artery after stent deployment is called in-stent restenosis (ISR). ISR is mainly due to neointimal hyperplasia, caused by increase in the vascular smooth muscle cells (VSMCs) proliferation, migration, extracellular matrix and collagen synthesis, and triggered by vessel injury during implantation [7]. 

Negative arterial remodeling, resulting from collagen deposition in the matrix and adventitia thickening, plays an important role in restenosis after balloon angioplasty. This is decreased by the use of BMS however, neointimal hyperplasia that results from the proliferation and migration of smooth muscle cells and extracellular matrix formation can still cause in-stent stenosis [29]. 

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