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Biointerface topography regulates phenotypic switching and cell apoptosis in vascular smooth muscle cells

Han, L., Yin, Q., Yang, L., van Rijn, P., Yang, Y., Liu, Y., Li, M., Yan, M., Zhou, Q., Yu, T. & Lian, Z., 4-Jun-2020, In : Biochemical and Biophysical Research Communications. 526, 3, p. 841-847 7 p.

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  • Biointerface topography regulates phenotypic switching and cell apoptosis in vascular smooth muscle cells

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Background: In-stent restenosis (ISR) is a complex disease that occurs after coronary stenting procedures. The development of quality materials and improvement of our understanding on significant factors regulating ISR are essential for enhancing prognosis. Vascular smooth muscle cells (VSMCs) are the main constituent cells of blood vessel walls, and dysfunction of VMSCs can exacerbate ISR. Accordingly, in this study, we explored the influence of wrinkled material topography on the biological functions of VSMCs.

Methods: Polydimethylsiloxane with a wrinkled topography was synthesized using elastomer base and crosslinking and observed by atomic force microscopy. VSMC proliferation, apoptosis, and morphology were determined by Cell Counting Kit-8 assays, fluorescence-assisted cell sorting, and phalloidin staining. alpha-Smooth muscle actin (alpha-SMA), major histocompatibility complex (MHC), and calponin 1 (CNN-1) expression levels were measured by quantitative real-time polymerase chain reaction and western blotting. Moreover, p53 and cleaved caspase-3 expression levels were evaluated by western blotting in VSMCs to assess apoptotic induction.

Results: Surface topographies were not associated with a clear orientation or elongation of VSMCs. The number of cells was increased on wrinkled surfaces (0.7 mu m in amplitude, and 3 mu m in wavelength [W3]) compared with that on other surfaces, contributing to continuously increased cell proliferation. Moreover, interactions of VSMCs with the W3 surface suppressed phenotypic switching, resulting in ISR via regulation of alpha-SMA, calponin-1, and SM-MHC expression. The surface with an amplitude of 0.05 mu m and a wavelength of 0.5 mu m (W0.5) promoted apoptosis by inducing caspase 3 and p53 activities.

Conclusion: Introduction of aligned topographies on biomaterial scaffolds could provide physical cues to modulate VSMC responses for engineering vascular constructs. Materials with wrinkled topographies could have applications in the development of stents to reduce ISR. (C) 2020 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)841-847
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume526
Issue number3
Early online date8-Apr-2020
Publication statusPublished - 4-Jun-2020

    Keywords

  • In-stent restenosis, Vascular smooth muscle cells, Phenotypic switching, Apoptosis, Wrinkled topography, Polydimethylsiloxane, STENT RESTENOSIS, OXIDATIVE STRESS, BIOLOGY

ID: 122003892