Project description:[original title] Gene expression response to the implantation of drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries. Different clinical outcomes have been observed for paclitaxel-eluting and bare metal cardiovascular stents. The aim of this project was to identify genes that might be associated with the observed clinical outcomes. Human left internal mammary artery (LIMA) was divided into three segments and and two of the segments were fitted with either a paclitaxel-eluting stent or a bare metal stent. The experiment includes three groups: control, paclitaxel-eluting stent, and bare metal stent, respectively. Each group includes four biological replicates (patients 1, 2, 4 and 5).
Project description:[original title] Gene expression response to the implantation of drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries. Different clinical outcomes have been observed for paclitaxel-eluting and bare metal cardiovascular stents. The aim of this project was to identify genes that might be associated with the observed clinical outcomes.
Project description:An unanticipated complication of the use of bare metal stents in percutaneous transluminal coronary angioplasty is in-stent restenosis resulting in >50% late lumen diameter loss in treated patients. In an effort to reduce in-stent restenosis, drug eluting stents containing the immunosuppressant sirolimus or zotarolimus have recently been developed. We report here the molecular response of arterial tissue to the implanting of these drug-eluting stents. Gene expression profiling was performed on 4 artery segments surrounding bare metal stents (BMS), 4 artery segments surrounding sirolimus-eluting stents (SES), and 4 artery segments surrounding zotarolimus-eluting stents (ZES) implanted into porcine animal models for 28 days.
Project description:An unanticipated complication of the use of bare metal stents in percutaneous transluminal coronary angioplasty is in-stent restenosis resulting in >50% late lumen diameter loss in treated patients. In an effort to reduce in-stent restenosis, drug eluting stents containing the immunosuppressant sirolimus or zotarolimus have recently been developed. We report here the molecular response of arterial tissue to the implanting of these drug-eluting stents.
Project description:Bare Metal Stents (BMS), Drug Eluting Stent (DES) and Exosomes Eluting Stent (EES) were placed in rat abdominal aorta for one week. Then total RNA of aortas was extracted. We used ScienCell's GeneQuery Rat Macrophage Polarization Markers qPCR Array Kit to quantitate gene expression of macrophage relevant genes.
Project description:Bare-metal (BMS) and drug-eluting stents (DES) were implanted in pig coronary arteries with an overstretch during coronary angioplasty under optical coherence tomography guidance. Arteries subjected to plain old balloon angioplasty (POBA) alone served as controls. Stented/balloon dilated segments were harvested 1, 3, 7, 14 and 28 days post-intervention for proteomics analysis. At day 28 all stented arteries showed a neointima formation covering the stent struts. The evolved neointima was separated from the media and analysed in a separate proteomics analysis. In total, 31 samples were analysed for the media by LC-MS/MS (n=3 BMS/DES at each time-point 1, 3, 7 and 28 days; n=4 POBA early [day1-day3] and n=3 POBA late [day 14 - day28]). For the neointima a total of 14 samples were analysed (n=7 BMS, n=7 DES at 28 days) including the neointima of arteries of a second cohort with 4 samples each for BMS and DES day 28. The neointima samples were run in duplicates.
Project description:Background: Drug-eluting stents (DES) have rapidly become a standard therapy for treatment of obstructive coronary artery disease. Differences exist in therapeutic responses to different DES formulations, and mechanisms to predict drug responses in the preclinical setting have not been standardized. Results: We have used gene expression profiling to characterize the patterns of gene regulation within cultures of rat aortic smooth muscle cells (RASMC) treated with rapamycin or paclitaxel, the two drugs widely used in commercially available DES. These studies further validate the use of the in vitro RASMC culture system as a model of insulin resistance. Gene expression profiles easily distinguish RASMC grown under normal or high glucose conditions, and we therefore followed this approach in order to understand the activity of these drugs under conditions that approximate those seen in type 2 diabetics. Remarkably, although both drugs are used to arrest smooth muscle proliferation when delivered by DES, there were major differences in gene regulatory responses. Paclitaxel caused marked changes in expression of tubulin-related genes, and also caused striking changes in the transcription of VEGF, PDGF, JAG-1 and their respective receptors, suggesting an important effect on paracrine and autocrine response to mitogens. However, the gene expression signatures elicited by paclitaxel showed little variation under different cell culture conditions. In contrast, these gene expression responses to rapamycin varied considerably depending on the glycemic conditions of culture, and rapamycin had a dramatic dose- and metabolic status- dependent effect on the transcription of key members of the AKT signaling axis, providing a transcriptional explanation for the paradoxical proliferative effect of rapamycin at low dose in the setting of high glucose concentrations and insulin resistance. Conclusions: Gene expression signatures for drugs eluted from coronary stents vary dramatically in ways that correlate with known differences in biological activities of these drugs. Gene expression profiling may provide a useful preclinical method to characterize the activities of candidate drugs for stent impregnation and to understand their biological activities. Keywords: Cardiovascular disease, drug eluting stent, vascular smooth muscle, rapamycin, paclitaxel
Project description:The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid, on the intracochlear FBR and electrical impedance post-implantation in a murine model. The left ears of CX3CR1+/GFP Thy1+/YFP (macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurement of electrical impedance. Dex-CI reduced electrical impedance and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggest that dexamethasone eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.
Project description:To investigate the effect of the dexamethasone-eluting electrode in the guinea pig cochlea, and compared the gene expression after 7 days insertion with that of a normal electrode or non-treated control by microarray. Male Hartley guinea pigs (SLC, Shizuoka, Japan) with an age of seven weeks were used for the study. Three were implanted with normal electrodes while three others received a dexamethasone-eluting electrode. The cochleae from two animals, which did not undergo surgery. Seven days after electrode implantation the whole temporal bone was removed and placed into RNAlater solution (Ambion, Life Technologies Co., Grand Island, NY) to stabilize and protect cellular RNA. The whole cochlea was dissected out under a microscope and total RNA were extracted.