Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers

Aim - The aim of the study was to determine the potential for KV1 potassium channel blockers as inhibitors of human neoinitimal hyperplasia. Methods and results - Blood vessels were obtained from patients or mice and studied in culture. Reverse transcriptasepolymerase chain reaction and immunocytochemistry were used to detect gene expression. Whole-cell patch-clamp, intracellular calcium measurement, cell migration assays, and organ culture were used to assess channel function.  KV1.3 was unique among the  KV1 channels in showing preserved and up-regulated expression when the vascular smooth muscle cells switched to the proliferating phenotype. There was strong expression in neointimal formations. Voltage-dependent potassium current in proliferating cells was sensitive to three different blockers of  KV1.3 channels. Calcium entry was also inhibited. All three blockers reduced vascular smooth muscle cell migration and the effects were non-additive. One of the blockers (margatoxin) was highly potent, suppressing cell migration with an IC of 85 pM. Two of the blockers were tested in organ-cultured human vein samples and both inhibited neointimal hyperplasia. Conclusion - KV1.3 potassium channels are functional in proliferating mouse and human vascular smooth muscle cells and have positive effects on cell migration. Blockers of the channels may be useful as inhibitors of neointimal hyperplasia and other unwanted vascular remodelling events. © 2010 The Author.

Consumption of bilberries controls gingival inflammation

Bioactive molecules in berries may be helpful in reducing the risk of oral diseases. The aim of this study was to determine the effect of bilberry consumption on the outcome of a routine dental clinical parameter of inflammation, bleeding on probing (BOP), as well as the impact on selected biomarkers of inflammation, such as cytokines, in gingival crevicular fluid (GCF) in individuals with gingivitis. Study individuals who did not receive standard of care treatment were allocated to either a placebo group or to groups that consumed either 250 or 500 g bilberries daily over seven days. The placebo group consumed an inactive product (starch). A study group, receiving standard of care (debridement only) was also included to provide a reference to standard of care treatment outcome. Cytokine levels were assayed using the Luminex MagPix system. The mean reduction in BOP before and after consumption of test product over 1 week was 41% and 59% in the groups that consumed either 250 or 500 g of bilberries/day respectively, and was 31% in the placebo group, and 58% in the standard of care reference group. The analysis only showed a significantreduction in cytokine levels in the group that consumed 500 g of bilberries/day. A statistically significant reduction was observed for IL-1β (p = 0.025), IL-6 (p = 0.012) and VEGF (p = 0.017) in GCF samples in the group that consumed 500 g of bilberries daily. It appears that berry intake has an ameliorating effect on some markers of gingival inflammation reducing gingivitis to a similar extent compared to standard of care.