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Objectives: We evaluated the effect of the different carrier systems on early vascular response through histological analysis and scanning electron microscopy using a porcine model.Background: Although Synergy™ and Promus PREMIER™ share an identical stent material and drug elution (everolimus), they use different drug carrier systems: biodegradable abluminal coating polymer or durable conformal coating polymer, respectively. However, data regarding the impact of the different coating systems on vessel healing are currently limited.Methods: Twelve Synergy™ and Promus PREMIER™ were implanted in 12 swine. Histopathological analysis of the stented segments was performed on the 2nd and 14th days after implantation. Morphometric analysis of the inflammation and intimal fibrin content was also performed.Results: On the 2nd day, neointimal thickness, percentage of neointimal area, and inflammatory and intimal fibrin content scores were not significantly different between the two groups. On the 14th day, the inflammatory and intimal fibrin content scores were significantly lower in Synergy™ versus those observed in Promus PREMIER™. In Synergy™, smooth muscle cells were found and the neointimal layers were smooth. In contrast, inflammatory cells were observed surrounding the struts of Promus PREMIER™.Conclusions: These results demonstrate that termination of reactive inflammation is accelerated after abluminal coating stent versus implantation of conformal coating stent. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the application of a novel enhanced device to retrieval of deployed stents in a porcine coronary model.Background: Recurrence of in-stent restenosis and stent thrombosis still remains to be resolved. Under these conditions, it is sometimes necessary to retrieve malfunctional stents responsible for thrombosis. However, few data exist regarding the feasibility and safety of retrieval device use in previously deployed coronary stents.Methods: We have developed an enhanced device consisting of an asymmetric forceps, conducting shaft (1.6 mm diameter, 150 cm length), and control handle. Bare-metal stents (3 mm diameter) were implanted in four pigs to create a malapposition model. Coronary artery injury was evaluated by intravascular ultrasound (IVUS) and histological imaging on the first and 14th days.Results: The device was delivered to the coronary artery using the existing catheter (7 Fr). After opening the forceps, the blade was forced into the space between the vessel wall and the stent, and the stent struts were then grasped with the forceps. This was then pulled back into the catheter, still grasping the stent struts with the forceps. All stents were successfully retrieved by this method (n = 4). On the first day, no apparent vessel wall injury was detectable by IVUS, although histological findings revealed damage to endothelial monolayer on retrieval of deployed stent. On the 14th day, mild intimal thickening was observed by IVUS and histology.Conclusions: These results demonstrate that the present device can be applied to transluminal retrieval of acquired malappositioned coronary stents. [ABSTRACT FROM AUTHOR]

The clinical implications of early and late endothelial progenitor cells (EPCs) in coronary artery disease (CAD) remain unclear. We investigated endothelial dysfunction in CAD by simultaneously examining early and late EPC colony formation and gene expression of specific surface markers in EPCs. EPCs were extracted from a total of 83 subjects with (n=47) and without (n=36) CAD. Early and late EPC colonies were formed from mononuclear cells extracted from peripheral blood. We found that fewer early EPC colonies were produced in the CAD group (7.2 ± 3.l/well) than those in the control group (12.4 ± 1.4/well, p<0.05), and more late EPC colonies were produced in the CAD group (0.8 ± 0.2/well) than those in the control group (0.25 ± 0.02/well, p<0.05). In the CAD group, the relative expression of CD31 and KDR of early and late EPCs was lower than in the control group. These results demonstrate that CAD patients could have increased late EPC density and that early and late EPCs in CAD patients exhibited immature endothelial characteristics. We suggest that changes in EPC colony count and gene expression of endothelial markers may have relation with development of CAD. [ABSTRACT FROM AUTHOR]

Gene correction of induced pluripotent stem cells (iPSCs) has therapeutic potential for treating homozygous familial hypercholesterolemia (HoFH) associated with low-density lipoprotein (LDL) receptor (LDLR) dysfunction. However, few data exist regarding the functional recovery and immunogenicity of LDLR gene-corrected iPSC-derived hepatocyte-like cells (HLCs) obtained from an HoFH patient. Therefore, we generated iPSC-derived HLCs from an HoFH patient harbouring a point mutation (NM_000527.4:c.901 G > T) in exon 6 of LDLR, and examined their function and immunogenicity. From the patient's iPSCs, one homozygous gene-corrected HoFH-iPSC clone and two heterozygous clones were generated using the CRISPR/Cas9 method. Both types of iPSC-derived HLCs showed recovery of the function of LDL uptake in immunofluorescence staining analysis. Furthermore, these gene-corrected iPSC-derived HLCs showed little immunogenicity against the patient's peripheral blood mononuclear cells in a cell-mediated cytotoxicity assay. These results demonstrate that LDL uptake of iPSC-derived HLCs from HoFH can be restored by gene correction without the appearance of further immunogenicity, suggesting that gene-corrected iPSC-derived HLCs are applicable to the treatment of HoFH. [ABSTRACT FROM AUTHOR]