Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the threedimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.
miR-22 exhibited excellent anti-lung cancer activity in vitro and in vivo, and post-transcriptional regulation of ErbB3 might be a potential mechanism.
Drug-eluting stents (DES) have become more widely used by cardiologists than bare metal stents (BMS) because of their better ability to control restenosis. However, recognized negative events, particularly including delayed or incomplete endothelialization and late stent thrombosis, have caused concerns over the long-term safety of DES. Although stent-based drug delivery can facilitate a drug's release directly to the restenosis site, a burst of drug release can seriously affect the pharmacological action and is a major factor accounting for adverse effects. Therefore, the drug release rate has become an important criterion in evaluating DES. The factors affecting the drug release rate include the drug carrier, drug, coating methods, drug storage, elution direction, coating thickness, pore size in the coating, release conditions (release medium, pH value, temperature), and hemodynamics after the stent implantation. A better understanding of how these factors influence drug release is particularly important for the reasonable use of efficient control strategies for drug release. This review summarizes the factors influencing the drug release from DES and presents strategies for enhancing the control of the drug's release, including the stent design, the application of absorbable stents, the development of new polymers, and the application of nanocarriers and improvements in the coating technology. Therefore, this paper provides a reference for the preparation of novel controlled slow-release DES.
In this study, we report the molecular characterization and functional analysis of OsLEA5 gene, which belongs to the atypical late embryogenesis abundant (LEA) group 5C from Oryza sativa L. The cDNA of OsLEA5 contains a 456 bp ORF encoding a polypeptide of 151 amino acids with a calculated molecular mass of 16.5 kDa and a theoretical pI of 5.07. The OsLEA5 polypeptide is rich in Leu (10%), Ser (8.6%), and Asp (8.6%), while Cys, Trp, and Gln residue contents are very low, which are 2, 1.3, and 1.3%, respectively. Bioinformatic analysis revealed that group 5C LEA protein subfamily contains a Pfam:LEA_2 domain architecture and is highly hydrophobic, intrinsically ordered with largely β-sheet and specific amino acid composition and distribution. Real-time PCR analysis showed that OsLEA5 was expressed in different tissue organs during different development stages of rice. The expression levels of OsLEA5 in the roots and panicles of full ripe stage were dramatically increased. The results of stress tolerance and cell viability assay demonstrated that recombinant E. coli cells producing OsLEA5 fusion protein exhibited improved resistance against diverse abiotic stresses: high salinity, osmotic, freezing, heat, and UV radiation. The OsLEA5 protein confers stabilization of the LDH under different abiotic stresses, such as heating, freeze-thawing, and drying in vitro. The combined results indicated that OsLEA5 protein was a hydrophobic atypical LEA and closely associated with resistance to multiple abiotic stresses. This research offered the valuable information for the development of crops with enhanced resistance to diverse stresses.
We studied the effects of gene transfection of endothelial cells with vascular endothelial growth factor (VEGF) on re-endothelialization and inhibition of in-stent restenosis. Transfected endothelial cells (ECs) exposed to different VEGF levels were seeded on a stent surface for evaluation in vitro. VEGF121(++) ECs and VEGF121(--) ECs were established using lentiviral-mediated HUVECs transfection. VEGF RNA transcription level and VEGF protein expression were detected by qPCR, Western blot, and ELISA. Methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, and in vitro HUVEC tube formation assay showed that VEGF overexpression promoted cell proliferation, migration, and endothelial capillary-like tube formation. Downregulation of VEGF expression inhibited these activities. Using a rotational culturing system, cells tightly adhered on the stent surface. Stents seeded with transfected ECs at different VEGF levels were implanted in abdominal aortas of New Zealand white rabbits to study re-endothelialization and inhibition of in-stent restenosis. Stents with cells exposed to excess VEGF expression were almost completely covered with cells after stent implantation for 1 week (w). In the VEGF interference group this process was delayed over 4 w due to RNAi-mediated silencing of VEGF. Cryosectioning after 12 w showed that stents seeded with HUVECs exposed to excess VEGF expression significantly reduced the neointima area and stenosis when compared with bare metal stents and stents from the VEGF interference group. Transgenic HUVECs were not found in tissues of experimental animals. Furthermore, cells from these tissues were similar to those from normal tissue. In conclusion, VEGF-mediated endothelialization was found. Furthermore, ECs exposed to VEGF overexpression reduced neointimal hyperplasia, promoted endothelialization, and reduced in-stent restenosis.
Compared with early bare-metal stents, drug-eluting stents (DESs) are more effective in treating coronary artery diseases, especially in inhibiting restenosis. However, in-stent restenosis still clinically occurs at a non-negligible rate. More importantly, delayed endothelialization, inflammation, and hypersensitivity trigger subacute or late adverse events, particularly stent thrombosis, and thereby raise more concerns over the long-term safety of DESs. These problems are mostly associated with the permanent polymeric materials, non-optimal therapeutic drugs, and/or metallic stent platforms used in current DES design. It is critically important to further improve and optimize DES design and apply newer strategies for developing next generation DES. These new generation DESs should maintain their clinical efficacy and meanwhile eliminate the long-term safety concerns. In this review article, the current information on the optimization of DES design was critically reviewed based on DES's basic components, namely, stent platform, restenotic drug, and polymer coating. The available strategies for designing next-generation DESs were also summarized, ranging from degradable polymer DESs, to polymer-free DESs, to fully biodegradable DESs.
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