scholarly journals Inducing highly physiologically relevant phenotypes of human vascular smooth muscle cells via 3D printing

2020 ◽  
Author(s):  
Peiran Zhu ◽  
Xuzhao Li ◽  
Wang Xin ◽  
Menglin Wang ◽  
Chengzhen Yin ◽  
...  

ABSTRACTVascular smooth muscle cells (vSMCs) are one of the essential cell types in blood vessel walls. A significant vSMC phenotype characteristic is that they collectively wrap around the outer layer of the healthy blood vessels with spindle-like morphology and help maintain the vascular tones and regulate the blood flow. Both physiological and biomedical research are impeded by the standard 2D cell culture approaches which do not create in vivo like microenvironment. Here, we systematically investigated the vSMCs culturing within 3D printed geometrical constraints and on printed microfilaments. Based on these models, we demonstrate a simple bioprinting approach for fast manufacturing vessel architectures with micro-grooved surfaces for vSMCs alignment. We validated that the vSMCs cultured on the printed vessel with microfilaments (VWMF) present a more physiologically relevant morphological phenotype and gene expression profile, and they are considerably more active in wound healing and ischemia than conventional planarly cultured vSMCs.

1994 ◽  
Vol 269 (11) ◽  
pp. 8504-8509
Author(s):  
K.A. Pritchard ◽  
M.K. O'Banion ◽  
J.M. Miano ◽  
N. Vlasic ◽  
U.G. Bhatia ◽  
...  

2005 ◽  
Vol 108 (6) ◽  
pp. 523-530 ◽  
Author(s):  
Giovanna CASTOLDI ◽  
Serena REDAELLI ◽  
Willy M. M. van de GREEF ◽  
Cira R. T. di GIOIA ◽  
Giuseppe BUSCA ◽  
...  

Ang II (angiotensin II) has multiple effects on vascular smooth muscle cells through the modulation of different classes of genes. Using the mRNA differential-display method to investigate gene expression in rat aortic smooth muscle cells in culture in response to 3 h of Ang II stimulation, we observed that Ang II down-regulated the expression of a member of the family of transmembrane receptors for Wnt proteins that was identified as Fzd2 [Fzd (frizzled)-2 receptor]. Fzds are a class of highly conserved genes playing a fundamental role in the developmental processes. In vitro, time course experiments demonstrated that Ang II induced a significant increase (P<0.05) in Fzd2 expression after 30 min, whereas it caused a significant decrease (P<0.05) in Fzd2 expression at 3 h. A similar rapid up-regulation after Ang II stimulation for 30 min was evident for TGFβ1 (transforming growth factor β1; P<0.05). To investigate whether Ang II also modulated Fzd2 expression in vivo, exogenous Ang II was administered to Sprague–Dawley rats (200 ng·kg−1 of body weight·min−1; subcutaneously) for 1 and 4 weeks. Control rats received normal saline. After treatment, systolic blood pressure was significantly higher (P<0.01), whereas plasma renin activity was suppressed (P<0.01) in Ang II- compared with the saline-treated rats. Ang II administration for 1 week did not modify Fzd2 expression in aorta of Ang II-treated rats, whereas Ang II administration for 4 weeks increased Fzd2 mRNA expression (P<0.05) in the tunica media of the aorta, resulting in a positive immunostaining for fibronectin at this time point. In conclusion, our data demonstrate that Ang II modulates Fzd2 expression in aortic smooth muscle cells both in vitro and in vivo.


2015 ◽  
Vol 37 (5) ◽  
pp. 1817-1829 ◽  
Author(s):  
Kai Huang ◽  
Zhi-Qiang Yan ◽  
Dan Zhao ◽  
Si-Guo Chen ◽  
Li-Zhi Gao ◽  
...  

Background/Aims: Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch. Methods and Results: Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including α-actin, calponin and SM22α, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect. Conclusion: Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis.


2007 ◽  
Vol 22 (2) ◽  
pp. 579-589 ◽  
Author(s):  
Daniel G. Sedding ◽  
Matthias Homann ◽  
Ulrike Seay ◽  
Harald Tillmanns ◽  
Klaus T. Preissner ◽  
...  

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 709-709
Author(s):  
Mizuo Mifune ◽  
Hiroyuki Sasamura ◽  
Hideaki Nakaya ◽  
Ryoko Shimizu-Hirota ◽  
Matsuhiko Hayashi ◽  
...  

P84 Previously, we and others have shown that angiotensin II enhances vascular smooth muscle cell extracellular matrix synthesis via stimulation of the type 1 angiotensin (AT1) receptor. Recently, expression of the type 2 (AT2) receptor has been confirmed in the adult vasculature, but its role in vascular remodeling has not yet been fully defined. In particular, conflicting data from in vivo studies have reported that AT2 receptor inhibition may either attenuate or enhance vascular hypertrophy and fibrosis. The aim of this study was to clarify the effects of direct stimulation of AT2 receptors on collagen synthesis in vascular smooth muscle cells in vitro. Firstly, retroviral gene transfer was used to supplement adult vascular smooth muscle cells with AT2 receptors to mimic the vasculature in vivo. Treatment of these cells with the AT2 receptor agonist CGP42212A (10-7 mol/L) alone did not cause a significant change in p42/p44 MAP kinase activity, but caused a modest (33%) decrease in protein tyrosine phosphatase activity. Treatment with CGP42112A also caused a dose- and time-dependent increase in both cell-associated and secretory collagen synthesis (148+17% of control at 48 h, p<0.05) which was completely inhibited by the AT2 receptor antagonist PD123319, but unaffected by the AT1 receptor antagonist losartan. The AT2 receptor-mediated stimulation of collagen synthesis was unaffected by tyrosine phosphatase inhibitors sodium orthovanadate and okadaic acid, but attenuated by pretreatment with pertussis toxin or Galphai antisense oligonuclotides. These results suggest that direct AT2 receptor stimulation can increase rather than decrease collagen synthesis in vascular smooth muscle cells, and suggest a role for Galphai in the AT2 receptor-mediated effects.


2020 ◽  
Vol 224 ◽  
pp. 40-54 ◽  
Author(s):  
Joaquim Bobi ◽  
Manel Garabito ◽  
NÚria Solanes ◽  
Pilar Cidad ◽  
Víctor Ramos-Pérez ◽  
...  

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