Whole genome expression analysis reveals differential effects of TiO2 nanotubes on vascular cells - PubMed (original) (raw)

Whole genome expression analysis reveals differential effects of TiO2 nanotubes on vascular cells

Lily Peng et al. Nano Lett. 2010 Jan.

Abstract

The response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to TiO2 nanotube arrays is studied through gene expression analysis. Microarrays revealed that nanotubes enhanced EC proliferation and motility, decreased VSMC proliferation, and decreased expression of molecules involved in inflammation and coagulation in both cell types. Networks generated from significantly affected genes suggest that cells may be sensing nanotopographical cues via pathways previously implicated in sensing shear stress.

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Figures

Figure 1

Figure 1

Nanotube effects on cellular functions and processes of ECs. List of significantly affected cellular functions identified by Ingenuity Pathway Analysis with p<0.005 (A). Identified functions are sorted into processes relevant to vascular device performance. Genes whose expression is significantly affected by nanotube arrays are plotted according to their likely effects on the four processes (B). Genes that promote a process are represented by open circles (○) with their y-axis on the left, while genes that inhibit a process are represented by filled-in circles (●) and have their y-axis on the right. Plotted this way, genes whose expression pattern is likely to promote a specific process (e.g. enhanced expression of a promoter of proliferation or reduced expression of a gene that inhibits proliferation) will appear on the top half of the graph, and those who would likely inhibit the process would appear on the bottom. Numbers at the top and bottom denote the number of genes that appear on the top or bottom region of the graph. For example, there are 15 EC genes whose expression pattern is consistent with a proliferative phenotype.

Figure 2

Figure 2

Top network of genes in ECs whose expression are significantly affected by exposure to nanotube arrays. Red indicates upregulation, green indicates downregulation. Intensity of color is proportional to magnitude of change. For the sake of simplicity, relationships between genes without a significant change in expression are not shown. See original network map in supplemental section, Figure S2.

Figure 3

Figure 3

Average expression levels of follistatin (FST), activating transcription factor 3 (ATF3), and early growth response 1 (EGR1) in ECs grown at low densities measured by quantitative PCR. Data is normalized by expression levels of each gene by ECs on flat surfaces and presented as average ± standard deviation. * p<0.05 when compared to flat controls, n=3.

Figure 4

Figure 4

Nanotube effects on cellular functions and processes of VSMCs. (A) List of significantly affected cellular functions identified by Ingenuity Pathway Analysis with p<0.005. Identified functions are sorted into processes relevant to vascular device performance. Genes whose expression is significantly affected by nanotube arrays are plotted according to their likely effects on the four processes (B), see figure 1 for more detailed explanation. Numbers at the top and bottom denote the number of genes that appear on the top or bottom region of the graph. For example, there are 33 genes whose expression patterns is consistent with a less proliferative phenotype.

Figure 5

Figure 5

Top network of genes in VSMCs whose expression are significantly affected by exposure to nanotube arrays. Red indicates upregulation, green indicates downregulation. Intensity of color is proportional to magnitude of change. For the sake of simplicity, relationships between genes without a significant change in expression are not shown. See original network map in supplemental section, Figure S3.

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