Biointerface topography regulates phenotypic switching and cell apoptosis in vascular smooth muscle cells.
Actins
/ genetics
Apoptosis
Biomechanical Phenomena
Calcium-Binding Proteins
/ genetics
Caspase 3
/ genetics
Cell Line
Cell Proliferation
Cells, Cultured
Cross-Linking Reagents
/ chemistry
Dimethylpolysiloxanes
/ chemistry
Gene Expression Regulation
Humans
Major Histocompatibility Complex
/ genetics
Microfilament Proteins
/ genetics
Microscopy, Atomic Force
Muscle, Smooth, Vascular
/ cytology
Phenotype
Surface Properties
Tissue Scaffolds
/ chemistry
Tumor Suppressor Protein p53
/ genetics
Calponins
Apoptosis
In-stent restenosis
Phenotypic switching
Polydimethylsiloxane
Vascular smooth muscle cells
Wrinkled topography
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
received:
19
02
2020
accepted:
05
03
2020
pubmed:
13
4
2020
medline:
18
12
2020
entrez:
13
4
2020
Statut:
ppublish
Résumé
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. 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. α-Smooth muscle actin (α-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. Surface topographies were not associated with a clear orientation or elongation of VSMCs. The number of cells was increased on wrinkled surfaces (0.7 μm in amplitude, and 3 μm 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 α-SMA, calponin-1, and SM-MHC expression. The surface with an amplitude of 0.05 μm and a wavelength of 0.5 μm (W0.5) promoted apoptosis by inducing caspase 3 and p53 activities. 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.
Sections du résumé
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. α-Smooth muscle actin (α-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 μm in amplitude, and 3 μm 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 α-SMA, calponin-1, and SM-MHC expression. The surface with an amplitude of 0.05 μm and a wavelength of 0.5 μm (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.
Identifiants
pubmed: 32278550
pii: S0006-291X(20)30517-9
doi: 10.1016/j.bbrc.2020.03.038
pii:
doi:
Substances chimiques
ACTA2 protein, human
0
Actins
0
Calcium-Binding Proteins
0
Cross-Linking Reagents
0
Dimethylpolysiloxanes
0
Microfilament Proteins
0
Tumor Suppressor Protein p53
0
baysilon
63148-62-9
CASP3 protein, human
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
841-847Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interests.