Der Effekt von Valproat auf die reaktive Zellproliferation und Migration von humanen koronaren Zellen
LizenzStandard (Fassung vom 01.10.2008)
This study investigates the effect of VPA on proliferation and migration in human coronary vascular cells. Methods and results: The theoretical clinical relevance of the data is estimated with a SI/MPL-ratio, which is defined as the relationship between a significant effect in vitro (SI) and the maximal plasma level in vivo (MPL). Cell culture: HUVEC, human umbilical endothelial cells; HCAEC, human coronary artery endothelial cells; HCMSMC, human coronary media smooth muscle cells. Proliferation assay: HUVEC, HCAEC, and HCMSMC were seeded as described. VPA was added in six different concentrations ranging between 50 and 300 µg/ml. At day 6 the cell number was calculated in relation with the cell number at day 1. Cell toxicity: Cytotoxic effects of VPA were studied in concentrations ranging from 50 to 300 µg/ml. Migration assay: Migration of HCMSMC after incubation with VPA in concentrations ranging from 50 to 300 µg/ml was studied for a period of 24 h. Proliferation assay: Strong dose-dependent antiproliferative effects were detected after 5 days of incubation with all the three tested cell types. In HUVEC, significant antiproliferative effects were found with VPA in concentrations of 100 µg/ml (P < 0.05, SI/MPL-ratio: 1.0) and more. In HCAEC and HCMSMC, significant antiproliferative effects were detected after incubation with VPA in the concentrations of 50 µg/ml (HCAEC: P < 0.01, SI/MPL ratio: 0.5; HCMSMC: P < 0.001, SI/MPL-ratio: 0.5). Migration assay: No effect on cell migration was detected after incubation of HCMSMC for a period of 48 h with VPA in concentrations ranging from 50 to 300 µg/ml. Cell toxicity: In HUVEC, HCAEC, and HCMSMC significant toxic effects were detected in all the VPA concentrations studied. Conclusion: Significant dose-dependent antiproliferative effects of VPA with SI/MPL ratios of 0.5 identify the drug as a promising candidate for both systemic and local therapy, such as drug eluting stents, of postinterventional restenosis.
Erstellung / Fertigstellung
OriginalpublikationCoronary artery disease 21 (2010), 5, S. 286 - 291
Normierte SchlagwörterProliferation [GND]
Cell movement [MeSH]
Valproic acid [MeSH]