Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS.

Thrombospondins (TSPs) are matricellular glycoproteins expressed in response to vascular injury. TSP-1 and TSP-2 are promotors of arterial remodeling while TSP-5 is believed to be protective. The current study assessed the differential effect of TSPs on protein expression in vascular smooth muscle cells (VSMCs). We hypothesized that TSP-1, TSP-2 and TSP-5 would regulate VSMC proteins involved in arterial remodeling. Human VSMCs were exposed to TSP-1, -2, -5 or serum free media (24 hours). Cell lysates were used to assess the targets TSP-1, TSP-2, TSP-5 and CD44), while the culture media was used to detect TGF-β1, PDGF-BB, ANGPTL-4 and IL-8. Statistical analysis was performed by t-test and p< 0.05 was considered significant. All TSPs increased their own expression and TSP-5 increased TSP-2. TSP-1 and TSP-2 increased production of ANGPTL-4 and PDGF-BB, while TSP-5 only increased ANGPTL-4. TSP-1 increased exclusively TGF-β1 and CD44 production. TSP-2 increased TSP-1 expression. All TSPs decreased IL-8. The findings suggest that TSP-1 and TSP-2 may promote vascular remodeling, in part, by increasing ANGPTL-4, PDGF-BB and their own expression. TSP-5 did not upregulate the inflammatory mediators TSP-1, PDGF-BB or TGF-β1, but upregulated its own expression, which could be a protective mechanism against the response to vascular injury.

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intimal hyperplasia (iH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. activation of HSP90 results in increased cell migration and proliferation. 17-n-allylamino-17-demethoxygeldanamycin (17-aaG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-dMaG) are low toxicity Food and drug association approved HSP90 inhibitors. The current study hypothesized that HSP90 inhibition was predicted to reduce vascular smooth muscle cell (VSMc) migration and proliferation. in addition, localized HSP90 inhibition may inhibit post-angioplasty iH formation. For proliferation, VSMcs were treated with serum-free media (SFM), 17-dMaG or 17-aaG. The selected proliferative agents were SFM, platelet derived growth factor (PDGF) or fibronectin. After three days, proliferation was measured. For migration, VSMcs were treated with SFM, 17-aaG or 17-dMaG with SFM, PdGF or fibronectin as chemoattractants. Balloon injury to the carotid artery was performed in rats. The groups included in the present study were the control, saline control, 17-dMaG in 20% pluronic gel delivered topically to the adventitia or intraluminal delivery of 17-DMAG. After 14 days, arteries were fixed and sectioned for morphometric analysis. data was analyzed using anoVa or a student's t-test. P<0.05 was considered to indicate a statistically significant difference. The results revealed that 17-AAG and 17-dMaG had no effect on cell viability. PdGF and fibronectin also increased VSMC proliferation and migration. Furthermore, both 17-aaG and 17-dMaG decreased cell migration and proliferation in all agonists. Topical adventitial treatment with 17-dMaG after balloon arterial injury reduced iH. HSP90 inhibitors suppressed VSMc proliferation and migration without affecting cell viability. Topical treatment with a HSP90 inhibitor (dMaG) decreased iH formation after arterial injury. it was concluded that 17-dMaG may be utilized as an effective therapy to prevent restenosis after revascularization.

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