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Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in various vascular diseases. Abnormal hemodynamic factors are important stimulus for promoting proliferation of VSMCs. In this study, we show that transmural pressure (TP) promotes the proliferation of human arterial smooth muscle cells (HASMCs) and its related mechanism. HASMCs were treated with different TPs (0,100,120,140,160,180 and 200 mmHg) in a custom-made pressure loading apparatus for 6 h. Results showed that proliferation of HASMCs was significantly promoted when the TP was over 160 mmHg compared with 0 mmHg (atmosphere pressure). In like manner, the expressions of NADPH oxidase 2(Nox2) and Survivin (SVV) and production of intracellular reactive oxygen species (ROS) were all elevated distinctly when TP exceeded 160 mmHg. Moreover, ROS scavenger NAC reduced TP-induced proliferation of HASMCs and expression of SVV largely, and slightly down-regulated expression of NOX2. NOX inhibitor apocynin (Apo) also significantly reduced TP-induced proliferation of HASMCs and expression of SVV and almost completely eliminated TP-induced production of ROS. These results demonstrate that TP drives proliferation of HASMCs via mechanism associated with NOX and SVV., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To assess the effects of survivin (SVV)in vascular endothelial cells., Methods: In this study, we applied a gain-of-function approach and ectopically expressed SVV in rat aortic endothelial cells (RAECs) using a SVV-expressing adenovirus. The resulting SVV expression on the steady-state mRNA and protein level in RAECs was determined by reverse transcription quantitative PCR and Western blot, respectively. Cell viability, apoptosis, and migration were assessed in vitro by CCK-8 assay, flow cytometry, and transwell assay, respectively. The effect of SVV on in vivo angiogenesis was evaluated by immunohistochemistry in nude mice. Non-infected RAECs and those infected with GFP-expressing control adenovirus were used as controls., Results: Compared to non-infected or control adenovirus-infected RAECs in vitro, SVV-expressing cells had increased viability and migratory capability, but reduced apoptosis. In vivo, SVV-expressing RAECs were associated with a higher level of angiogenesis., Conclusion: SVV is a positive regulator of endothelial cell survival and migration, and thus, stabilizes endothelial cells and stimulates angiogenesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Platelet-derived growth factor (PDGF) is known to induce phenotypic switching of vascular smooth muscle cells (VSMCs) from contractile to a pathological synthetic state, which played an essential role in proliferation of VSMCs. Sonic hedgehog (Shh) contributes to the proliferation of VSMCs when induced by PDGF. Here, we investigated the probable role of Shh in PDGF-induced VSMC dedifferentiation and its underlying mechanisms. We found that PDGF stimulated Shh expression in VSMCs, which was mediated by activation of PDGFRβ/ERK1/2 cell signaling pathway. Further, we found PDGF-induced VSMC phenotypic modulation was accompanied by up-regulation of Shh/Gli family zinc finger 2 (Gli2) signaling and Krüppel-like factor 4 (KLF4). When inhibited Shh in the presence of PDGF, the expressions of KLF4 and VSMC dedifferentiation markers were down-regulated and the effect of PDGF in inducing VSMC dedifferentiation was blocked. In the absence of PDGF, Shh signaling activation increased the expression of KLF4 and promoted VSMC dedifferentiation. The results indicate Shh participated in the regulation of PDGF-induced VSMC dedifferentiation. Finally, we found that KLF4 was closely involved in this process. On inhibition of KLF4, PDGF induced VSMC dedifferentiation was abrogated, even in the presence of Shh. Taken together, the results provide critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The long-term patency rates in vascular transplants (diameter<3.0-4.0mm) are very low due to thrombus formation and intimal hyperplasia. A possible mechanism is the loss of the endothelial cells (ECs) lining. Previous attempts to reseed ECs had poor results due to seeded cell loss, severe antigenicity, and low compliance. The objectives of this study were to generate an allogeneic vascular substitution with autogenic ECs and low antigenicity., Methods: ECs from mongrels were obtained and multiplied in vitro, then seeded to the allogeneic vein luminal surface, which was preserved by freeze-drying radiation. The cultivated cells' secretory function was confirmed by von Willebrand factor detection. The allogeneic vascular was then transplanted into animals' necks in situ. The physical properties, EC state, and vascular structure of the allogeneic vascular grafts were studied., Results: The secretory function of ECs did not vary in vitro. The expression level of MHC-II antigen in freeze-dried radiation-treated vasculature was lower than normal fresh vasculature (P<0.05). ECs covered the vascular inner surface and adhered tightly after implantation. As assessed by scanning electron micrograph, most ECs adhered tightly, and the cell polarity changed in accordance with the direction of the force. Allograft blood vessels with autogenic ECs implanted showed significant decreases in both thrombosis and intimal hyperplasia., Conclusion: Allograft blood vessels seeded with autogenic ECs improved the patency of small-diameter grafts in a canine model. Our study showed a significant decrease in both thrombosis and intimal hyperplasia., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)