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Rapid endothelialization of cardiovascular stents is critical to prevent major clinical complications such as restenosis. Reconstruction of the native endothelium on the stent surface can be achieved by the capture of endothelial progenitor cells (EPCs) or neighboring endothelial cells (ECs) in vivo. In this study, stainless steel cardiovascular stents were functionalized with recombinant scFv antibody fragments specific for vascular endothelial growth factor receptor‐2 (VEGFR2) that is expressed on EPCs and ECs. Anti‐VEGFR2 scFvs were expressed in glycosylated form in Escherichia coli and covalently attached to amine‐functionalized, titania‐coated steel disks and stents. ScFv‐coated surfaces exhibited no detectable cytotoxicity to human ECs or erythrocytes in vitro and bound 15 times more VEGFR2‐positive human umbilical vein ECs than controls after as little as 3 min. Porcine coronary arteries were successfully stented with scFv‐coated stents with no adverse clinical events after 30 days. Endovascular imaging and histology revealed coverage of the anti‐VEGFR2 scFv‐coated stent with a cell layer after 5 days and the presence of a neointima layer with a minimum thickness of 80 μm after 30 days. Biofunctionalization of cardiovascular stents with endothelial cell‐capturing antibody fragments in this manner offers promise in accelerating stent endothelialization in vivo. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:213–224, 2020. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are a major cause of mortality in patients with psoriatic arthritis (PsA), but the precise mechanism of increased cardiovascular risk is unknown. Endothelial dysfunction plays a crucial role in the development of atherosclerosis. Circulating endothelial progenitor cells (CEPCs) contribute to endothelial regeneration and their level may be affected by chronic inflammation. The aim of this study was to evaluate the number of CEPCs in patients with PsA (n = 24) compared with controls (n = 26). CEPCs were identified as CD133+/ KDR+ cells in peripheral blood, using flow cytometry. A significantly decreased number of CEPCs was observed in patients with PsA (p < 0.0001). The number of these cells was significantly, inversely correlated with the severity of skin and joint involvement (Psoriasis Area and Severity Index (PASI), DAS28) and the level of C-reactive protein. We hypothesize that the reduced number of CEPCs may indicate and contribute to the increased cardiovascular risk in patients with PsA. [ABSTRACT FROM AUTHOR]

Background: Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells., Materials and Methods: Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated. Inhibition of P-glycoprotein transport activity was monitored by flow cytometry. Changes in intracellular doxorubicin accumulation were observed by means of fluorescence microscopy., Results: Latilagascene B was demonstrated to be an effective P-glycoprotein inhibitor, able to increase doxorubicin accumulation in resistant cells, however not able to restore doxorubicin cytotoxicity in LoVo/Dx cells., Conclusion: The structure of latilagascene B seems to be an interesting candidate for further synthesis of new derivatives of reduced cytotoxicity and high anti-MDR potency., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Introduction: Cardiovascular mortality is significantly increased in patients with chronic kidney disease (CKD). The number of circulating endothelial progenitor cells (EPCs) may affect vascular regenerative potential and thus influence cardiovascular mortality., Objectives: The aim of the study was to assess the number of circulating EPCs and the factors that potentially affect these cells, including vascular endothelial growth factor (VEGF) and endostatin, in patients with CKD., Patients and Methods: The study involved 139 patients divided into groups depending on the severity of renal impairment: 67 predialysis patients with CKD, 46 patients on hemodialysis (HD), and 26 patients on peritoneal dialysis (PD). Plasma levels of VEGF and endostatin were measured by enzyme-linked immunosorbent assays. The number of circulating EPCs, defined as CD34+VEGFR2+, was assessed in the whole blood using flow cytometry., Results: There was a positive correlation between VEGF and CD34+VEGFR2+ and the glomerular filtration rate. Endostatin levels increased with renal impairment. The highest endostatin levels were observed in HD and PD patients. The number of EPCs was significantly lower in predialysis patients with CKD and in HD patients, while in PD patients it was nonsignificantly lower compared with the control group., Conclusions: In patients with CKD, a decrease in circulating EPCs may impair vascular regenerative potential and thus contribute to a higher cardiovascular risk. The effect of significantly increased endostatin levels on the endothelial function and progenitors in patients with CKD requires further investigation.

Background: The search for promising modulators of cancer multidrug resistance (MDR) that are able to reduce the activity of P-glycoprotein, thus restoring the cytotoxicity of anticancer drugs, is ongoing. The identification of compounds that overcome the apoptosis deficiency that frequently accompanies MDR is also of great therapeutic importance., Materials and Methods: Four stilbenes, resveratrol, piceatannol and its two derivatives, were tested for their MDR-modulating and apoptosis-inducing activity in drug-sensitive (LoVo) and doxorubicin-resistant human adenocarcinoma cell line (LoVo/Dx) by means of flow cytometry and fluorescence microscopy., Results: Trans-3,5,3',4'-tetramethoxystilbene (PicMet) was identified as a promising modulator that efficiently increased accumulation of both rhodamine 123 and doxorubicin inside resistant cells. It also increased sensitivity of LoVo/Dx cells to doxorubicin. Resveratrol and trans-3,5,3',4'-tetracetoxystilbene (PicAcet) were identified as apoptosis inducers in LoVo/Dx cells., Conclusion: The stilbene structure may constitute a promising chemical scaffold for the synthesis of potential MDR modulators.

The choice of cell lines for multidrug resistance (MDR) modulators screening may affect the results obtained. Screening is most often performed in model systems which employ cell lines derived from haematological malignancies. Cell lines originating from solid tumours are far less popular. In the present work, we aimed to test the usefulness of the drug-sensitive human sarcoma cell line MES-SA, and its multidrug-resistant counterpart MES-SA/Dx5, as a model system for modulators' anti-MDR potency evaluation. Overexpression of P-glycoprotein in the resistant but not in the sensitive cell line was confirmed by flow cytometry and confocal microscopy. Flow cytometry demonstrated that verapamil and trifluoperazine reduced MDR in MES-SA/Dx5 cells as assessed by the rhodamine 123 accumulation test. Both modulators also restored in MES-SA/Dx5 cells the drug accumulation pattern typical for sensitive cells, as judged by confocal microscopy. We conclude that the MES-SA and MES-SA/Dx5 cell line pair constitute a good model for MDR modulators study.