curcumin and Neointima

Curcumin has been shown to affect platelet-derived growth factor (PDGF)- and tumor necrosis factor (TNF)-α-elicited vascular smooth muscle cell (VSMC) migration and inhibit neointima formation following vascular injury. However, whether two other curcuminoids isolated from Curcuma longa, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), also demonstrate antimigratory activity in VSMCs similar to that of curcumin remain uncharacterized.. Based on 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and proliferating cell nuclear antigen immunostaining analyses as well as changes in intima/media ratios, we show that DMC exhibits more potent effects than the other curcuminoids. We aimed to evaluate the effects and characterize the molecular mechanisms of DMC on VSMC migration and neointima formation in a carotid injury model. DMC decreased the expression of matrix metalloproteinase 2/9 and inhibited VSMC migration as demonstrated by in vitro scratch wound and transwell assays. Furthermore, DMC may inhibit the migration of VSMCs by reducing the expression of matrix metalloproteinase 2/9 via downregulation of the focal adhesion kinase/phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) and phosphoglycerate kinase 1/extracellular signal regulated kinase 1/2 signaling pathways. Using a rat carotid arterial injury model, we show that DMC treatment was more potent than treatment with the other curcuminoids with respect to reducing intima/media ratios and the number of proliferating cells.. DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.

Topics: Angioplasty, Balloon; Animals; Cell Adhesion; Cell Movement; Cell Proliferation; Curcuma; Curcumin; Diarylheptanoids; Down-Regulation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinase 3; Muscle, Smooth, Vascular; Neointima; Phosphatidylinositol 3-Kinase; Phosphoglycerate Kinase; Phosphorylation; Proliferating Cell Nuclear Antigen; Protein Disulfide-Isomerases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation.. ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects.. ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group.. The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.

Topics: Animals; Coated Materials, Biocompatible; Coronary Stenosis; Coronary Vessels; Curcuma; Endothelium, Vascular; Inflammation; Microscopy, Electron, Scanning; Neointima; Prosthesis Implantation; Stents; Sus scrofa; Time Factors