Biomedical subjects

Felix Vogt

Publications and source records attributed to Felix Vogt.

7 recordsLinked to original sources

PubMed2006

A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells.

OBJECTIVES: Novel stents loaded with an integrin-binding cyclic Arg-Gly-Asp peptide (cRGD) were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting endothelial progenitor cells (EPCs). BACKGROUND: Re-endothelialization is important for healing after arterial injury. METHODS: Effects of cRGD on EPC number, recruitment in flow, and invasion were analyzed in vitro. A durable polymer coating containing 67 microg cRGD per stent was developed for Guidant Tetra stents. Twelve cRGD-loaded polymer, 12 unloaded polymer, and 12 bare metal stents were deployed in porcine coronary arteries. Quantification of cRGD in peri-stent tissue was established by high-performance liquid chromatography (HPLC) and mass spectrometry (MS). Histomorphometry and immunostaining were performed after 4 and 12 weeks. Recruitment of labeled porcine EPCs was assessed 7 days after intracoronary infusion. RESULTS: The cRGD clearly supported the outgrowth, recruitment, and migration of EPCs in vitro. At 4 weeks, there was no difference for mean neointimal area and percent area stenosis in the cRGD-loaded, polymer, or bare metal stent group. At 12 weeks, neointimal area (2.2 +/- 0.3 mm2) and percent area stenosis (33 +/- 5%) were significantly reduced compared with polymer stents (3.8 +/- 0.4 mm2, 54 +/- 6%; p = 0.010) or bare metal stents (3.8 +/- 0.3 mm2, 53 +/- 3%; p < 0.001). The HPLC/MS confirmed cRGD tissue levels of 1 to 3 mug/stent at 4 weeks, whereas cRGD was not detectable at 12 weeks. Staining for CD34 and scanning electron microscopy indicated enhanced endothelial coverage on cRGD-loaded stents at 4 weeks associated with a significant increase in the early recruitment of infused EPCs. CONCLUSIONS: Stent coating with cRGD may be useful for reducing in-stent restenosis by accelerating endothelialization.

Animals↗

PubMed2004

Downregulation of N-cadherin in the neointima stimulates migration of smooth muscle cells by RhoA deactivation.

OBJECTIVE: The aim of the study was to analyze whether cadherin- and Rho-family GTPases-mediated dynamic rearrangement of cell-cell adhesion play an important role during human arterial smooth muscle cell (haSMC) migration. METHODS: Expression patterns of N-cadherin and beta-catenin were analyzed in a domestic pig restenosis model after 14, 28, and 90 days as well as in quiescent and migratory haSMCs in vitro. N-cadherin expression was upregulated by transient sense; downregulation was induced by antisense transfection. For functional inhibition, antibody GC-4 was used. Cell migration was quantified using Boyden chamber assays. Regulation of RhoA GTPase was tested by assessment of RhoA activity. RESULTS: In vivo analysis of N-cadherin expression in a porcine restenosis model revealed downregulation in the neointima after 14 days. After 28 days, N-cadherin expression was slightly restored, while after 90 days, no difference between medial and neointimal expression was detectable. beta-Catenin levels remained unchanged during the whole period. According to the in vivo situation, N-cadherin was significantly downregulated in migratory haSMCs compared to quiescent cells in vitro. After N-cadherin overexpression, haSMC migration was reduced by 87% (P<0.001). By contrast, inhibition of N-cadherin in quiescent haSMCs by GC-4 increased the migratory potential by 87% (P<0.01). In haSMCs overexpressing N-cadherin, a significant upregulation of RhoA activity was demonstrated, while RhoA activity was blocked by GC-4. CONCLUSIONS: These results indicate that the regulation of haSMC attachment by N-cadherins is essential for haSMC migration. Modification of N-cadherin expression and activity induces RhoA signaling with relevance for the reorganization of the actin cytoskeleton.

Animals↗

PubMed2004

Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent.

AIM: The aim of this study was to assess technical feasibility, biocompatibility, and impact on coronary stenosis of a new biodegradable paclitaxel-loaded polylactide stent. Due to high rates of in-stent restenosis and permanent nature of metal stent implants, synthetic polymers have been proposed as surrogate materials for stents and local delivery systems for drugs. Paclitaxel was shown to inhibit vascular smooth muscle cell proliferation and migration. METHODS AND RESULTS: A novel biodegradable double-helical stent was manufactured using controlled expansion of saturated polymers (CESP) for the moulding of a bioresorbable poly(D,L)-lactic acid (PDLLA). A modified balloon catheter for stent deployment was developed according to the mechanical stent properties. Twelve paclitaxel-loaded (170 microg) polylactide stents, 12 unloaded polylactide stents, and 12 316L bare metal stents were deployed in porcine coronary arteries of 36 animals. Six pigs of each group were sacrificed after 3 weeks and 3 months, respectively, for every setting. Drug release kinetics as well as histomorphometrical and histopathological analyses were performed. A slow paclitaxel release kinetic for more than 2 months and therapeutic tissue concentrations were demonstrated. Coronary stenosis after implantation of paclitaxel-loaded stents (30+/-5% or 49+/-4%) was significantly inhibited compared to unloaded PDLLA stents (65+/-10%, P=0.021 or 71+/-4%, P=0.004) and metal stents (53+/-6% or 68+/-8%, P=0.029 and P=0.020) after 3 weeks or 3 months. Early complete endothelialisation was shown. Nevertheless, a local inflammatory response to the polylactide as a result of the polymer resorption process was observed. CONCLUSIONS: This novel polylactide stent showed sufficient mechanic stability, and by incorporation of paclitaxel, a significant potential to reduce restenosis development after vascular intervention was seen.

Animals↗

PubMed2004

Coronary artery stents in multislice computed tomography: in vitro artifact evaluation.

RATIONALE AND OBJECTIVE: The aim of this study was to systematically compare the ability to assess the coronary artery lumen in the presence of coronary artery stents in multislice spiral CT (MSCT). METHODS: Ten different coronary artery stents were examined with 4- and 16-detector row MSCT scanners. For image reconstruction, a standard and a dedicated convolution kernel for coronary artery stent visualization were used. Images were analyzed regarding lumen visibility, intraluminal attenuation, and artifacts outside the stent lumen. Results were compared using repeated-measure analysis of variance. RESULTS: Depending on stent type, scanner hardware, and convolution kernel, artificial lumen narrowing ranged from 20% to 100%. The convolution kernel had the most significant influence on the visibility of the stent lumen. Artificial lumen narrowing and intraluminal attenuation changes decreased significantly using the dedicated convolution kernel. In general, most severe artifacts were caused by gold or gold-coated stents. CONCLUSIONS: Independent of the scanner hardware or dedicated convolution kernels, routine evaluation of most coronary artery stents is not yet feasible using MSCT.

Analysis of Variance↗

PubMed2003

Activated platelets trigger an inflammatory response and enhance migration of aortic smooth muscle cells.

OBJECTIVE: Exposure of the subendothelium to flowing blood following rupture of atherosclerotic lesions or during balloon angioplasty initiates platelet adhesion to the vascular wall. Because activated platelets release proinflammatory mediators (e.g., interleukin (IL)-1beta) and secrete growth factors, platelet adhesion to the subendothelial matrix might contribute to the recruitment of inflammatory cells and promote migration and proliferation of vascular smooth muscle cells (SMCs). METHODS AND RESULTS: Here, we demonstrate that incubation of cultured monolayers of aortic SMCs with alpha-thrombin-activated platelets significantly enhances the secretion of monocyte chemoattractant protein-1 (MCP-1) (P<0.05) and promotes SMC migration (P<0.05). Platelet-induced secretion of MCP-1 was abolished by anti-IL-1alpha and beta monoclonal antibodies or the IL-1 receptor antagonist (IL-1RA). In contrast, platelet-mediated SMC migration was attenuated only by anti-platelet-derived growth factor (PDGF)-mAb but not by IL-1RA. Correspondingly, recombinant human interleukin-1 (rhIL-1) beta increased MCP release by SMCs but had no effect on SMC migration. Platelet-mediated MCP secretion by SMCs involved the activation and nuclear translocation of the transcription factor nuclear factor-kappaB (NF-kappaB). CONCLUSION: Therefore, platelet adhesion to the subendothelium increases the chemotactic and migratory properties of SMC and is likely to contribute substantially to the process of atherosclerosis and vessel (re-)stenosis.

Aorta↗

PubMed2002

Decrease of vascular smooth muscle cell locomotion by abciximab, but not tirofiban: a possible role of different affinity to alpha v beta 3 integrins.

AIM: The EPISTENT and EPIC studies demonstrated a reduction of clinically driven re-interventions after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation in patients treated with abciximab, while for tirofiban no similar effects could be demonstrated. This may be explained by the different effects on the migratory and invasive potential of vascular smooth muscle cells (VSMCs) by integrin alpha v beta 3 blockade. Therefore, the objective of this study was to compare the effectiveness of abciximab and tirofiban to affect VSMC migration and invasion. METHODS: Vascular smooth muscle cells were treated with abciximab (0.1-1 microg/ml), tirofiban (0.1-1 microg/ml), and the alpha v beta 3 specific antibody LM609 (1-5 microg/ml), that was used as a positive control during the assay (treatment) over 24 h before the assay (pre-treatment), or before and during the assay (combined treatment). Sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxyy-6-nitro) benzene sulfonic acid (XTT)-assay and cell counting measured the influence of the substances on VSMC proliferation. Using a Boyden Chamber model, the capability of VSMCs for migration and invasion was tested with different chemo-attractants and barriers. RESULTS: Any influence of the platelet glycoprotein (GP) IIb/IIIa receptor (integrin alpha IIb beta 3) antagonists on VSMC proliferation could be excluded. After combined treatment, abciximab demonstrated a dose-dependent inhibition of migration (IC50 = 33 microg/ml) and invasion (IC50 = 0.5 microg/ml) of VSMCs. Administration during the assay without pre-treatment inhibited migration similarly (IC50 = 32 microg/ml) but invasion to a significant lower extent (IC50 = 44 microg/ml). Administration of tirofiban during the assay with or without pre-treatment had no inhibitory effect on VSMC migration and invasion. Pre-treatment alone with one of the substances also did not alter VSMC migration or invasion. CONCLUSION: Abciximab administration in physiological concentrations was capable of significantly inhibiting the migratory and invasive potential of VSMCs, while for tirofiban no similar effect could be demonstrated.

Abciximab↗

PubMedDate not supplied

Characterization of differential gene expression in quiescent and invasive human arterial smooth muscle cells.

Proliferation, migration and invasion of smooth muscle cells (SMCs) are essential pathogenic processes in the development of a broad spectrum of cardiovascular disorders, like arteriosclerosis, restenosis after percutaneous transluminal angioplasty and stent implantation as well as transplant vessel disease. As an in vitro model mimicking these processes, the Boyden chamber was employed to characterize the diverging migratory and invasive potentials of proliferating and nonproliferating human arterial SMCs (haSMCs). Using this model, differential gene expression of both phenotypes was analyzed by a cDNA array system (Clontech human cardiovascular array). With these arrays, 558 cardiovascular-associated genes could be compared. Further, gene expression was exactly quantified by real-time RT-PCR. Protein expression was analyzed by ELISA and Western blotting. In total, 47 genes were differentially expressed more than 1.5 times. Most of the differentially regulated genes in this study were associated with the extracellular matrix (ECM) and cell motility. In detail, the respective groups were matrix-organizing proteins, ECM proteins, cell adhesion proteins, extracellular communication and cytoskeleton motility proteins. Genes known to be differentially regulated during haSMC migration and invasion, like TIMP 2, TIMP 3, and MMP 3, were confirmed by the array data. Reduced expression of several cytoskeletal proteins, like vimentin, fibronectin, cytokeratins and beta1 integrin, was shown in the invasive phenotype. Further, angio-associated protein, alpha E-catenin and atrial brain natriuretic peptide receptor were downregulated whereas TFPI 2 was strongly upregulated in invasive haSMCs. In conclusion, several relevant potential candidate genes for the quiescent and the invasive SMC phenotype were identified and genes already known to be differentially regulated by previous analysis were confirmed.

Arteriosclerosis↗